2024-03-29T10:10:32Zhttp://repository.helmholtz-hzi.de/oai/requestoai:repository.helmholtz-hzi.de:10033/1211022019-08-30T11:33:57Zcom_10033_620613col_10033_620614
Philippi, C
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500
Loretz, B
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Schaefer, U F
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500
Lehr, C M
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Department of Biopharmaceutics and Pharmaceutical Technology, Saarland University, Saarbrücken, Germany.
2011-02-03T12:41:35Z
2011-02-03T12:41:35Z
2010-09-01
Telomerase as an emerging target to fight cancer--opportunities and challenges for nanomedicine. 2010, 146 (2):228-40 J Control Release
1873-4995
20381558
10.1016/j.jconrel.2010.03.025
http://hdl.handle.net/10033/121102
Journal of controlled release : official journal of the Controlled Release Society
Telomerase as an enzyme is responsible for the renewal of the chromosomal ends, the so-called telomeres. By preventing them from shortening with each cell cycle, telomerase is able to inhibit cellular senescence and apoptosis. Telomerase activity, which is detectable in the majority of cancer cells, allows them to maintain their proliferative capacity. The thus obtained immortality of those cells again is a key to their malignancy. Based on these discoveries, it is obvious that telomerase inhibitors would represent an innovative approach to fight cancer, and a variety of such candidate molecules are currently in the pipeline. Telomerase inhibitors largely fall in two classes of compounds: small synthetic molecules and nucleotide-based biologicals. For several candidates, some proof of concept studies have been demonstrated, either on cell cultures or in animal models. But the same studies also revealed that inefficient delivery is largely limiting the translational step into the clinic. The most appealing feature of telomerase inhibitors, which distinguishes them from conventional anticancer drugs, is probably seen in their intrinsic non-toxicity to normal cells. Nevertheless, efficient delivery to the target cells, i.e. to the tumor, is still required. Here, some well-known biopharmaceutical problems such as insufficient solubility, permeability or even metabolic stability are frequently encountered. To address these challenges, there is a clear need for adequate delivery technologies, for example by using nanomedicines, that would allow to overcome their biopharmaceutical shortcomings and to warrant a sufficient bioavailability at the target side. This review first briefly explains the concept of telomerase and telomerase inhibition in cancer therapy. It secondly aims to provide an overview of the different currently known telomerase inhibitors. Finally, the biopharmaceutical limitations of these molecules are discussed as well as the possibilities to overcome those limits by novel drug carrier systems and formulation approaches.
en
Animals
Antineoplastic Agents
Drug Delivery Systems
Enzyme Inhibitors
Humans
Nanomedicine
Neoplasms
Telomerase
Telomerase as an emerging target to fight cancer--opportunities and challenges for nanomedicine.
article
2018-06-13T19:26:29Z
Telomerase as an enzyme is responsible for the renewal of the chromosomal ends, the so-called telomeres. By preventing them from shortening with each cell cycle, telomerase is able to inhibit cellular senescence and apoptosis. Telomerase activity, which is detectable in the majority of cancer cells, allows them to maintain their proliferative capacity. The thus obtained immortality of those cells again is a key to their malignancy. Based on these discoveries, it is obvious that telomerase inhibitors would represent an innovative approach to fight cancer, and a variety of such candidate molecules are currently in the pipeline. Telomerase inhibitors largely fall in two classes of compounds: small synthetic molecules and nucleotide-based biologicals. For several candidates, some proof of concept studies have been demonstrated, either on cell cultures or in animal models. But the same studies also revealed that inefficient delivery is largely limiting the translational step into the clinic. The most appealing feature of telomerase inhibitors, which distinguishes them from conventional anticancer drugs, is probably seen in their intrinsic non-toxicity to normal cells. Nevertheless, efficient delivery to the target cells, i.e. to the tumor, is still required. Here, some well-known biopharmaceutical problems such as insufficient solubility, permeability or even metabolic stability are frequently encountered. To address these challenges, there is a clear need for adequate delivery technologies, for example by using nanomedicines, that would allow to overcome their biopharmaceutical shortcomings and to warrant a sufficient bioavailability at the target side. This review first briefly explains the concept of telomerase and telomerase inhibition in cancer therapy. It secondly aims to provide an overview of the different currently known telomerase inhibitors. Finally, the biopharmaceutical limitations of these molecules are discussed as well as the possibilities to overcome those limits by novel drug carrier systems and formulation approaches.
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2019-08-30 11:33:57.582
Helmholtz Zentrum für Infektionsforschung Repository
hzi@openrepository.com
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oai:repository.helmholtz-hzi.de:10033/1461522019-08-30T11:33:57Zcom_10033_620613col_10033_620614
Schulze, Christine
9834c5e7bc2ace062db3f3b452c7c868
500
Schaefer, Ulrich F
4d014124ac1d9ed6e002598ffdf56f21
500
Ruge, Christian A
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500
Wohlleben, Wendel
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500
Lehr, Claus-Michael
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500
Department of Biopharmaceutics and Pharmaceutical Technology, Saarland University, Saarbruecken, Germany. chr.schulze@mx.uni-saarland.de
2011-10-20T11:24:33Z
2011-10-20T11:24:33Z
2011-04
Interaction of metal oxide nanoparticles with lung surfactant protein A. 2011, 77 (3):376-83 Eur J Pharm Biopharm
1873-3441
21056657
10.1016/j.ejpb.2010.10.013
http://hdl.handle.net/10033/146152
European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft für Pharmazeutische Verfahrenstechnik e.V
The alveolar lining fluid (ALF) covering the respiratory epithelium of the deep lung is the first biological barrier encountered by nanoparticles after inhalation. We here report for the first time significant differences for metal oxide nanoparticles to the binding of surfactant protein A (SP-A), the predominant protein component of ALF. SP-A is a physiologically most relevant protein and provides important biological signals. Also, it is involved in the lung's immune defence, controlling e.g. particle binding, uptake or transcytosis by epithelial cells and macrophages. In our study, we could prove different particle-protein interaction for eight different nanoparticles, whereas particles of the same bulk material revealed different adsorption patterns. In contrast to other proteins as bovine serum albumin (BSA), SP-A does not seem to significantly deagglomerate large agglomerates of particles, indicating different adsorption mechanisms as in the well-investigated model protein BSA. These findings may have important consequences for biological fate and toxicological effects of inhaled nanomaterials.
en
Adsorption
Animals
Blotting, Western
Bronchoalveolar Lavage Fluid
Electrophoresis, Polyacrylamide Gel
Lung
Metals
Microscopy, Electron, Transmission
Nanoparticles
Oxides
Particle Size
Protein Binding
Pulmonary Surfactant-Associated Protein A
Surface Properties
Swine
Ultracentrifugation
Interaction of metal oxide nanoparticles with lung surfactant protein A.
Article
2018-05-23T10:17:25Z
The alveolar lining fluid (ALF) covering the respiratory epithelium of the deep lung is the first biological barrier encountered by nanoparticles after inhalation. We here report for the first time significant differences for metal oxide nanoparticles to the binding of surfactant protein A (SP-A), the predominant protein component of ALF. SP-A is a physiologically most relevant protein and provides important biological signals. Also, it is involved in the lung's immune defence, controlling e.g. particle binding, uptake or transcytosis by epithelial cells and macrophages. In our study, we could prove different particle-protein interaction for eight different nanoparticles, whereas particles of the same bulk material revealed different adsorption patterns. In contrast to other proteins as bovine serum albumin (BSA), SP-A does not seem to significantly deagglomerate large agglomerates of particles, indicating different adsorption mechanisms as in the well-investigated model protein BSA. These findings may have important consequences for biological fate and toxicological effects of inhaled nanomaterials.
ORIGINAL
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2019-08-30 11:33:57.55
Helmholtz Zentrum für Infektionsforschung Repository
hzi@openrepository.com
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oai:repository.helmholtz-hzi.de:10033/1969722019-08-30T11:33:05Zcom_10033_620613col_10033_620614
Le Guével, Xavier
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Daum, Nicole
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Schneider, Marc
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Pharmaceutical Nanotechnology, Saarland University, Saarbrücken, Germany.
2011-12-13T13:53:35Z
2011-12-13T13:53:35Z
2011-07-08
Synthesis and characterization of human transferrin-stabilized gold nanoclusters. 2011, 22 (27):275103 Nanotechnology
1361-6528
21613679
10.1088/0957-4484/22/27/275103
http://hdl.handle.net/10033/196972
Nanotechnology
Human transferrin has been biolabelled with gold nanoclusters (Au NCs) using a simple, fast and non-toxic method. These nanocrystals (<2 nm) are stabilized in the protein via sulfur groups and have a high fluorescence emission in the near infrared region (QY=4.3%; λem=695 nm). Structural investigation and photophysical measurements show a high population of clusters formed of 22-33 gold atoms covalently bound to the transferrin. In solutions with pH ranging from 5 to 10 and in buffer solutions (PBS, HEPES), those biolabelled proteins exhibit a good stability. No significant quenching effect of the fluorescent transferrin has been detected after iron loading of iron-free transferrin (apoTf) and in the presence of a specific polyclonal antibody. Additionally, antibody-induced agglomeration demonstrates no alteration in the protein activity and the receptor target ability. MTT and Vialight® Plus tests show no cytotoxicity of these labelled proteins in cells (1 µg ml(-1)-1 mg ml(-1)). Cell line experiments (A549) indicate also an uptake of the iron loaded fluorescent proteins inside cells. These remarkable data highlight the potential of a new type of non-toxic fluorescent transferrin for imaging and targeting.
en
Synthesis and characterization of human transferrin-stabilized gold nanoclusters.
Article
2018-06-12T18:05:51Z
Human transferrin has been biolabelled with gold nanoclusters (Au NCs) using a simple, fast and non-toxic method. These nanocrystals (<2 nm) are stabilized in the protein via sulfur groups and have a high fluorescence emission in the near infrared region (QY=4.3%; λem=695 nm). Structural investigation and photophysical measurements show a high population of clusters formed of 22-33 gold atoms covalently bound to the transferrin. In solutions with pH ranging from 5 to 10 and in buffer solutions (PBS, HEPES), those biolabelled proteins exhibit a good stability. No significant quenching effect of the fluorescent transferrin has been detected after iron loading of iron-free transferrin (apoTf) and in the presence of a specific polyclonal antibody. Additionally, antibody-induced agglomeration demonstrates no alteration in the protein activity and the receptor target ability. MTT and Vialight® Plus tests show no cytotoxicity of these labelled proteins in cells (1 µg ml(-1)-1 mg ml(-1)). Cell line experiments (A549) indicate also an uptake of the iron loaded fluorescent proteins inside cells. These remarkable data highlight the potential of a new type of non-toxic fluorescent transferrin for imaging and targeting.
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2019-08-30 11:33:05.36
Helmholtz Zentrum für Infektionsforschung Repository
hzi@openrepository.com
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oai:repository.helmholtz-hzi.de:10033/2375932019-08-30T11:33:57Zcom_10033_620613col_10033_620614
Krejci, I
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Piana, C
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Howitz, S
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Wegener, T
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Fiedler, S
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Zwanzig, M
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Schmitt, D
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Daum, N
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Meier, K
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Lehr, C M
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Batista, U
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Zemljic, S
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Messerschmidt, J
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Franzke, J
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Wirth, M
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Gabor, F
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Department of Pharmaceutical Technology and Biopharmaceutics, University of Vienna, Althanstraße 14, A-1090 Vienna, Austria.
2012-08-07T14:16:09Z
2012-08-07T14:16:09Z
2012-03
Process optimization and biocompatibility of cell carriers suitable for automated magnetic manipulation. 2012, 8 (3):1239-47 Acta Biomater
1878-7568
21925622
10.1016/j.actbio.2011.08.031
http://hdl.handle.net/10033/237593
Acta biomaterialia
There is increasing demand for automated cell reprogramming in the fields of cell biology, biotechnology and the biomedical sciences. Microfluidic-based platforms that provide unattended manipulation of adherent cells promise to be an appropriate basis for cell manipulation. In this study we developed a magnetically driven cell carrier to serve as a vehicle within an in vitro environment. To elucidate the impact of the carrier on cells, biocompatibility was estimated using the human adenocarcinoma cell line Caco-2. Besides evaluation of the quality of the magnetic carriers by field emission scanning electron microscopy, the rate of adherence, proliferation and differentiation of Caco-2 cells grown on the carriers was quantified. Moreover, the morphology of the cells was monitored by immunofluorescent staining. Early generations of the cell carrier suffered from release of cytotoxic nickel from the magnetic cushion. Biocompatibility was achieved by complete encapsulation of the nickel bulk within galvanic gold. The insulation process had to be developed stepwise and was controlled by parallel monitoring of the cell viability. The final carrier generation proved to be a proper support for cell manipulation, allowing proliferation of Caco-2 cells equal to that on glass or polystyrene as a reference for up to 10 days. Functional differentiation was enhanced by more than 30% compared with the reference. A flat, ferromagnetic and fully biocompatible carrier for cell manipulation was developed for application in microfluidic systems. Beyond that, this study offers advice for the development of magnetic cell carriers and the estimation of their biocompatibility.
en
Archived with thanks to Acta biomaterialia
Caco-2 Cells
Cell Adhesion
Cell Proliferation
Gold
Humans
Magnetics
Magnets
Materials Testing
Microfluidic Analytical Techniques
Nickel
Process optimization and biocompatibility of cell carriers suitable for automated magnetic manipulation.
Article
2018-06-13T01:20:15Z
There is increasing demand for automated cell reprogramming in the fields of cell biology, biotechnology and the biomedical sciences. Microfluidic-based platforms that provide unattended manipulation of adherent cells promise to be an appropriate basis for cell manipulation. In this study we developed a magnetically driven cell carrier to serve as a vehicle within an in vitro environment. To elucidate the impact of the carrier on cells, biocompatibility was estimated using the human adenocarcinoma cell line Caco-2. Besides evaluation of the quality of the magnetic carriers by field emission scanning electron microscopy, the rate of adherence, proliferation and differentiation of Caco-2 cells grown on the carriers was quantified. Moreover, the morphology of the cells was monitored by immunofluorescent staining. Early generations of the cell carrier suffered from release of cytotoxic nickel from the magnetic cushion. Biocompatibility was achieved by complete encapsulation of the nickel bulk within galvanic gold. The insulation process had to be developed stepwise and was controlled by parallel monitoring of the cell viability. The final carrier generation proved to be a proper support for cell manipulation, allowing proliferation of Caco-2 cells equal to that on glass or polystyrene as a reference for up to 10 days. Functional differentiation was enhanced by more than 30% compared with the reference. A flat, ferromagnetic and fully biocompatible carrier for cell manipulation was developed for application in microfluidic systems. Beyond that, this study offers advice for the development of magnetic cell carriers and the estimation of their biocompatibility.
ORIGINAL
Krejci et al_final.pdf
Krejci et al_final.pdf
original manuscript
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2019-08-30 11:33:57.421
Helmholtz Zentrum für Infektionsforschung Repository
hzi@openrepository.com
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oai:repository.helmholtz-hzi.de:10033/2471512019-08-30T11:34:47Zcom_10033_620613col_10033_620614
Hankin, Steve
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500
Boraschi, Diana
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Duschl, Albert
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Lehr, Claus-Michael
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500
Lichtenbeld, Hera
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2012-10-05T10:59:37Z
2012-10-05T10:59:37Z
2012-10-05
Towards nanotechnology regulation – Publish the unpublishable 2011, 6 (3):228 Nano Today
17480132
10.1016/j.nantod.2011.03.002
http://hdl.handle.net/10033/247151
Nano Today
http://linkinghub.elsevier.com/retrieve/pii/S1748013211000272
Archived with thanks to Nano Today
Towards nanotechnology regulation – Publish the unpublishable
Article
2018-06-13T00:37:43Z
ORIGINAL
Hankin et al_final.pdf
Hankin et al_final.pdf
original manuscript
application/pdf
301512
https://hzi.openrepository.com/bitstream/10033/247151/1/Hankin%20et%20al_final.pdf
f89a832e6c026be9fe95f847209b86dc
MD5
1
true
CC-LICENSE
license_url
license_url
text/plain
49
https://hzi.openrepository.com/bitstream/10033/247151/2/license_url
c0b3e2a72fe5e4b72fa5798bb22cd3a3
MD5
2
false
license_text
license_text
application/octet-stream
0
https://hzi.openrepository.com/bitstream/10033/247151/3/license_text
d41d8cd98f00b204e9800998ecf8427e
MD5
3
false
license_rdf
license_rdf
application/octet-stream
24332
https://hzi.openrepository.com/bitstream/10033/247151/4/license_rdf
306824103cdab5a2460a7737d9c97e69
MD5
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LICENSE
license.txt
license.txt
text/plain
1685
https://hzi.openrepository.com/bitstream/10033/247151/5/license.txt
cb598eeb10bfed09d26fd8d285172ad4
MD5
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false
TEXT
Hankin et al_final.pdf.txt
Hankin et al_final.pdf.txt
Extracted Text
text/plain
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https://hzi.openrepository.com/bitstream/10033/247151/8/Hankin%20et%20al_final.pdf.txt
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MD5
8
false
THUMBNAIL
Hankin et al_final.pdf.jpg
Hankin et al_final.pdf.jpg
Generated Thumbnail
image/jpeg
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https://hzi.openrepository.com/bitstream/10033/247151/9/Hankin%20et%20al_final.pdf.jpg
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MD5
9
false
elsevier-thumbnail.png
application/octet-stream
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https://hzi.openrepository.com/bitstream/10033/247151/10/elsevier-thumbnail.png
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MD5
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10033/247151
oai:hzi.openrepository.com:10033/247151
2019-08-30 11:34:47.729
Helmholtz Zentrum für Infektionsforschung Repository
hzi@openrepository.com
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oai:repository.helmholtz-hzi.de:10033/2481112019-08-30T11:25:11Zcom_10033_620613col_10033_620614
May, Sabine
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500
Jensen, Birte
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500
Wolkenhauer, Markus
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500
Schneider, Marc
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500
Lehr, Claus Michael
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600
http://orcid.org/0000-0002-5864-8462
PharmBioTec GmbH, Saarbrücken, Germany.
2012-10-10T12:30:38Z
2012-10-10T12:30:38Z
2012-08
Dissolution techniques for in vitro testing of dry powders for inhalation. 2012, 29 (8):2157-66 Pharm. Res.
1573-904X
22528980
10.1007/s11095-012-0744-2
http://hdl.handle.net/10033/248111
Pharmaceutical research
To evaluate different dissolution testing methods and subsequently develop a simple to perform but reproducible and discriminating dissolution technique for inhalative powders.
en
Archived with thanks to Pharmaceutical research
Dissolution techniques for in vitro testing of dry powders for inhalation.
Article
2013-08-15T00:00:00Z
To evaluate different dissolution testing methods and subsequently develop a simple to perform but reproducible and discriminating dissolution technique for inhalative powders.
ORIGINAL
May et al_final.pdf
May et al_final.pdf
original manuscript
application/pdf
716886
https://hzi.openrepository.com/bitstream/10033/248111/1/May%20et%20al_final.pdf
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MD5
1
true
Supplementary info May.pdf
Supplementary info May.pdf
supplementary material
application/pdf
218599
https://hzi.openrepository.com/bitstream/10033/248111/2/Supplementary%20info%20May.pdf
ce1a8f6540ac059e53dd45bb4d66d81c
MD5
2
false
CC-LICENSE
license_url
license_url
text/plain
49
https://hzi.openrepository.com/bitstream/10033/248111/3/license_url
c0b3e2a72fe5e4b72fa5798bb22cd3a3
MD5
3
false
license_text
license_text
application/octet-stream
0
https://hzi.openrepository.com/bitstream/10033/248111/4/license_text
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MD5
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license_rdf
license_rdf
application/octet-stream
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https://hzi.openrepository.com/bitstream/10033/248111/5/license_rdf
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MD5
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false
LICENSE
license.txt
license.txt
text/plain
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https://hzi.openrepository.com/bitstream/10033/248111/6/license.txt
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MD5
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TEXT
Supplementary info May.pdf.txt
Supplementary info May.pdf.txt
Extracted Text
text/plain
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https://hzi.openrepository.com/bitstream/10033/248111/11/Supplementary%20info%20May.pdf.txt
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MD5
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false
May et al_final.pdf.txt
May et al_final.pdf.txt
Extracted Text
text/plain
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https://hzi.openrepository.com/bitstream/10033/248111/12/May%20et%20al_final.pdf.txt
873c3e7b0a21cc0f3cc0a0375810319b
MD5
12
false
THUMBNAIL
May et al_final.pdf.jpg
May et al_final.pdf.jpg
Generated Thumbnail
image/jpeg
27850
https://hzi.openrepository.com/bitstream/10033/248111/14/May%20et%20al_final.pdf.jpg
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MD5
14
false
Supplementary info May.pdf.jpg
Supplementary info May.pdf.jpg
Generated Thumbnail
image/jpeg
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https://hzi.openrepository.com/bitstream/10033/248111/15/Supplementary%20info%20May.pdf.jpg
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MD5
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10033/248111
oai:hzi.openrepository.com:10033/248111
2019-08-30 11:25:11.104
Helmholtz Zentrum für Infektionsforschung Repository
hzi@openrepository.com
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oai:repository.helmholtz-hzi.de:10033/2659722019-08-30T11:28:24Zcom_10033_620613col_10033_620614
Jacobs, Simone
122afd2fb52245625cfadc2aaadacaf0
500
Bunt, Craig R
7fc37872af22795192c87e4e969f0441
500
Wu, Zimei
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500
Lehr, Claus-Michael
e25b30ba80302580419199334c0f4c6b
500
Rupenthal, Ilva D
e1cd1fd2a8ed42f84227b359b1800ca8
500
Biopharmaceutics and Pharmaceutical Technology, Saarland University, Saarbrücken, Germany.
2013-01-18T11:46:16Z
2013-01-18T11:46:16Z
2012-11
Characterization and evaluation of β-glucan formulations as injectable implants for protein and peptide delivery. 2012, 38 (11):1337-43 Drug Dev Ind Pharm
1520-5762
22300392
10.3109/03639045.2011.650646
http://hdl.handle.net/10033/265972
Drug development and industrial pharmacy
Injectable implants are biodegradable, syringeable formulations that are injected as liquids, but form a gel inside the body due to a change in pH, ions or temperature.
en
Archived with thanks to Drug development and industrial pharmacy
Characterization and evaluation of β-glucan formulations as injectable implants for protein and peptide delivery.
Article
2013-11-15T00:00:00Z
Injectable implants are biodegradable, syringeable formulations that are injected as liquids, but form a gel inside the body due to a change in pH, ions or temperature.
ORIGINAL
Jacobs et al_final.pdf
Jacobs et al_final.pdf
original manuscript
application/pdf
266274
https://hzi.openrepository.com/bitstream/10033/265972/1/Jacobs%20et%20al_final.pdf
29e48c582db4a07155f4b9090e9f5604
MD5
1
true
Jacobs et al - Figure 1.pdf
Jacobs et al - Figure 1.pdf
figure 1
application/pdf
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Jacobs et al_final.pdf.txt
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Extracted Text
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THUMBNAIL
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Generated Thumbnail
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MD5
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Jacobs et al - Figure 1.pdf.jpg
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Generated Thumbnail
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10033/265972
oai:hzi.openrepository.com:10033/265972
2019-08-30 11:28:24.083
Helmholtz Zentrum für Infektionsforschung Repository
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oai:repository.helmholtz-hzi.de:10033/2665132019-08-30T11:34:22Zcom_10033_620613col_10033_620614
Dandekar, Prajakta
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Jain, Ratnesh
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Keil, Manuel
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Loretz, Brigitta
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Muijs, Leon
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Schneider, Marc
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500
Auerbach, Dagmar
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Jung, Gregor
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Lehr, Claus-Michael
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Wenz, Gerhard
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Department of Drug Delivery, Helmholtz-Institute for Pharmaceutical Research Saarland, Helmholtz-Center for Infection Research (HZI), Saarland University, D-66123 Saarbrücken, Germany.
2013-01-22T15:26:29Z
2013-01-22T15:26:29Z
2012-12-28
Cellular delivery of polynucleotides by cationic cyclodextrin polyrotaxanes. 2012, 164 (3):387-93 J Control Release
1873-4995
22789529
10.1016/j.jconrel.2012.06.040
http://hdl.handle.net/10033/266513
Journal of controlled release : official journal of the Controlled Release Society
Cationic polyrotaxanes, obtained by temperature activated threading of cationic cyclodextrin derivatives onto water-soluble cationic polymers (ionenes), form metastable nanometric polyplexes with pDNA and combinations of siRNA with pDNA. Because of their low toxicity, the polyrotaxane polyplexes constitute a very interesting system for the transfection of polynucleotides into mammalian cells. The complexation of Cy3-labeled siRNA within the polyplexes was demonstrated by fluorescence correlation spectroscopy. The uptake of the polyplexes (red) was imaged by confocal fluorescence microscopy using the A549 cell line as a model (blue: nuclei, green: membranes). The results prove the potential of polyrotaxanes for further investigations involving knocking down genes of therapeutic interest.
en
Archived with thanks to Journal of controlled release : official journal of the Controlled Release Society
Cellular delivery of polynucleotides by cationic cyclodextrin polyrotaxanes.
Article
2018-06-12T23:12:10Z
Cationic polyrotaxanes, obtained by temperature activated threading of cationic cyclodextrin derivatives onto water-soluble cationic polymers (ionenes), form metastable nanometric polyplexes with pDNA and combinations of siRNA with pDNA. Because of their low toxicity, the polyrotaxane polyplexes constitute a very interesting system for the transfection of polynucleotides into mammalian cells. The complexation of Cy3-labeled siRNA within the polyplexes was demonstrated by fluorescence correlation spectroscopy. The uptake of the polyplexes (red) was imaged by confocal fluorescence microscopy using the A549 cell line as a model (blue: nuclei, green: membranes). The results prove the potential of polyrotaxanes for further investigations involving knocking down genes of therapeutic interest.
ORIGINAL
Dandekar et al_final.pdf
Dandekar et al_final.pdf
original manuscript
application/pdf
2749355
https://hzi.openrepository.com/bitstream/10033/266513/1/Dandekar%20et%20al_final.pdf
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CC-LICENSE
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https://hzi.openrepository.com/bitstream/10033/266513/2/license_url
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license_text
license_text
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LICENSE
license.txt
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TEXT
Dandekar et al_final.pdf.txt
Dandekar et al_final.pdf.txt
Extracted Text
text/plain
40316
https://hzi.openrepository.com/bitstream/10033/266513/8/Dandekar%20et%20al_final.pdf.txt
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MD5
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false
THUMBNAIL
Dandekar et al_final.pdf.jpg
Dandekar et al_final.pdf.jpg
Generated Thumbnail
image/jpeg
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https://hzi.openrepository.com/bitstream/10033/266513/9/Dandekar%20et%20al_final.pdf.jpg
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MD5
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elsevier-thumbnail.png
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10033/266513
oai:hzi.openrepository.com:10033/266513
2019-08-30 11:34:22.368
Helmholtz Zentrum für Infektionsforschung Repository
hzi@openrepository.com
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oai:repository.helmholtz-hzi.de:10033/2758922019-08-30T11:34:21Zcom_10033_620613col_10033_620614
Hansen, Steffi
6bb9ae2a7d6ae348419e78349d92c93f
500
Lehr, Claus-Michael
e25b30ba80302580419199334c0f4c6b
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Schaefer, Ulrich F
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2013-03-25T15:19:29Z
2013-03-25T15:19:29Z
2013-02
Modeling the human skin barrier--towards a better understanding of dermal absorption. 2013, 65 (2):149-51 Adv. Drug Deliv. Rev.
1872-8294
23266369
10.1016/j.addr.2012.12.002
http://hdl.handle.net/10033/275892
Advanced drug delivery reviews
en
Archived with thanks to Advanced drug delivery reviews
Modeling the human skin barrier--towards a better understanding of dermal absorption.
Article
2018-06-13T04:15:39Z
ORIGINAL
Hansen et al_final.pdf
Hansen et al_final.pdf
original manuscript
application/pdf
441880
https://hzi.openrepository.com/bitstream/10033/275892/1/Hansen%20et%20al_final.pdf
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MD5
1
true
CC-LICENSE
license_url
license_url
text/plain
49
https://hzi.openrepository.com/bitstream/10033/275892/2/license_url
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MD5
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false
license_text
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application/octet-stream
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https://hzi.openrepository.com/bitstream/10033/275892/3/license_text
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MD5
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https://hzi.openrepository.com/bitstream/10033/275892/4/license_rdf
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MD5
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LICENSE
license.txt
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text/plain
1685
https://hzi.openrepository.com/bitstream/10033/275892/5/license.txt
cb598eeb10bfed09d26fd8d285172ad4
MD5
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false
TEXT
Hansen et al_final.pdf.txt
Hansen et al_final.pdf.txt
Extracted Text
text/plain
12049
https://hzi.openrepository.com/bitstream/10033/275892/8/Hansen%20et%20al_final.pdf.txt
6d96b94eef0eec9849428cd8997e9191
MD5
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THUMBNAIL
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Generated Thumbnail
image/jpeg
27323
https://hzi.openrepository.com/bitstream/10033/275892/9/Hansen%20et%20al_final.pdf.jpg
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MD5
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10033/275892
oai:hzi.openrepository.com:10033/275892
2019-08-30 11:34:21.501
Helmholtz Zentrum für Infektionsforschung Repository
hzi@openrepository.com
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oai:repository.helmholtz-hzi.de:10033/2759922019-08-30T11:25:43Zcom_10033_620613col_10033_620614
Hansen, Steffi
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500
Lehr, Claus-Michael
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Schaefer, Ulrich F
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Drug Delivery, Helmholtz Institute for Pharmaceutical Research Saarland (HIPS), Helmholtz-Center for Infection Research (HZI), Saarbruecken, Germany. Steffi.hansen@helmholtz-hzi.de
2013-03-26T10:35:22Z
2013-03-26T10:35:22Z
2013-02
Improved input parameters for diffusion models of skin absorption. 2013, 65 (2):251-64 Adv. Drug Deliv. Rev.
1872-8294
22626979
10.1016/j.addr.2012.04.011
http://hdl.handle.net/10033/275992
Advanced drug delivery reviews
To use a diffusion model for predicting skin absorption requires accurate estimates of input parameters on model geometry, affinity and transport characteristics. This review summarizes methods to obtain input parameters for diffusion models of skin absorption focusing on partition and diffusion coefficients. These include experimental methods, extrapolation approaches, and correlations that relate partition and diffusion coefficients to tabulated physico-chemical solute properties. Exhaustive databases on lipid-water and corneocyte protein-water partition coefficients are presented and analyzed to provide improved approximations to estimate lipid-water and corneocyte protein-water partition coefficients. The most commonly used estimates of lipid and corneocyte diffusion coefficients are also reviewed. In order to improve modeling of skin absorption in the future diffusion models should include the vertical stratum corneum heterogeneity, slow equilibration processes, the absorption from complex non-aqueous formulations, and an improved representation of dermal absorption processes. This will require input parameters for which no suitable estimates are yet available.
en
Archived with thanks to Advanced drug delivery reviews
Improved input parameters for diffusion models of skin absorption.
Article
2018-06-13T21:24:03Z
To use a diffusion model for predicting skin absorption requires accurate estimates of input parameters on model geometry, affinity and transport characteristics. This review summarizes methods to obtain input parameters for diffusion models of skin absorption focusing on partition and diffusion coefficients. These include experimental methods, extrapolation approaches, and correlations that relate partition and diffusion coefficients to tabulated physico-chemical solute properties. Exhaustive databases on lipid-water and corneocyte protein-water partition coefficients are presented and analyzed to provide improved approximations to estimate lipid-water and corneocyte protein-water partition coefficients. The most commonly used estimates of lipid and corneocyte diffusion coefficients are also reviewed. In order to improve modeling of skin absorption in the future diffusion models should include the vertical stratum corneum heterogeneity, slow equilibration processes, the absorption from complex non-aqueous formulations, and an improved representation of dermal absorption processes. This will require input parameters for which no suitable estimates are yet available.
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2019-08-30 11:25:43.381
Helmholtz Zentrum für Infektionsforschung Repository
hzi@openrepository.com
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oai:repository.helmholtz-hzi.de:10033/2931602019-08-30T11:33:57Zcom_10033_620613col_10033_620614
Gómez-Mantilla, José-David
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500
Casabó, Vicente Germán
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500
Schaefer, Ulrich F
4d014124ac1d9ed6e002598ffdf56f21
500
Lehr, Claus-Michael
e25b30ba80302580419199334c0f4c6b
500
Biopharmaceutics and Pharmaceutical Technology, Saarland University, Campus A4.1, D-66123 Saarbruecken, Germany.
2013-05-31T14:18:18Z
2013-05-31T14:18:18Z
2013-01-30
Permutation Test (PT) and Tolerated Difference Test (TDT): two new, robust and powerful nonparametric tests for statistical comparison of dissolution profiles. 2013, 441 (1-2):458-67 Int J Pharm
1873-3476
23194886
10.1016/j.ijpharm.2012.11.008
http://hdl.handle.net/10033/293160
International journal of pharmaceutics
The most popular way of comparing oral solid forms of drug formulations from different batches or manufacturers is through dissolution profile comparison. Usually, a similarity factor known as (f2) is employed; However, the level of confidence associated with this method is uncertain and its statistical power is low. In addition, f2 lacks the flexibility needed to perform in special scenarios. In this study two new statistical tests based on nonparametrical Permutation Test theory are described, the Permutation Test (PT), which is very restrictive to confer similarity, and the Tolerated Difference Test (TDT), which has flexible restrictedness to confer similarity, are described and compared to f2. The statistical power and robustness of the tests were analyzed by simulation using the Higuchi, Korsmayer, Peppas and Weibull dissolution models. Several batches of oral solid forms were simulated while varying the velocity of dissolution (from 30 min to 300 min to dissolve 85% of the total content) and the variability within each batch (CV 2-30%). For levels of variability below 10% the new tests exhibited better statistical power than f2 and equal or better robustness than f2. TDT can also be modified to distinguish different levels of similarity and can be employed to obtain customized comparisons for specific drugs. In conclusion, two new methods, more versatile and with a stronger statistical basis than f2, are described and proposed as viable alternatives to that method. Additionally, an optimized time sampling strategy and an experimental design-driven strategy for performing dissolution profile comparisons are described.
en
Archived with thanks to International journal of pharmaceutics
Permutation Test (PT) and Tolerated Difference Test (TDT): two new, robust and powerful nonparametric tests for statistical comparison of dissolution profiles.
Article
2018-06-13T20:04:12Z
The most popular way of comparing oral solid forms of drug formulations from different batches or manufacturers is through dissolution profile comparison. Usually, a similarity factor known as (f2) is employed; However, the level of confidence associated with this method is uncertain and its statistical power is low. In addition, f2 lacks the flexibility needed to perform in special scenarios. In this study two new statistical tests based on nonparametrical Permutation Test theory are described, the Permutation Test (PT), which is very restrictive to confer similarity, and the Tolerated Difference Test (TDT), which has flexible restrictedness to confer similarity, are described and compared to f2. The statistical power and robustness of the tests were analyzed by simulation using the Higuchi, Korsmayer, Peppas and Weibull dissolution models. Several batches of oral solid forms were simulated while varying the velocity of dissolution (from 30 min to 300 min to dissolve 85% of the total content) and the variability within each batch (CV 2-30%). For levels of variability below 10% the new tests exhibited better statistical power than f2 and equal or better robustness than f2. TDT can also be modified to distinguish different levels of similarity and can be employed to obtain customized comparisons for specific drugs. In conclusion, two new methods, more versatile and with a stronger statistical basis than f2, are described and proposed as viable alternatives to that method. Additionally, an optimized time sampling strategy and an experimental design-driven strategy for performing dissolution profile comparisons are described.
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oai:repository.helmholtz-hzi.de:10033/2944432019-08-30T11:33:30Zcom_10033_620613col_10033_620614
Franzen, Lutz
5f33be5c546581114e94404e7ed886f8
500
Vidlářová, Lucie
05b0bcfa1c63b0d0a5600bd137deed40
500
Kostka, Karl-Heinz
ecb1b92cde26510adb4549580650f7cc
500
Schaefer, Ulrich F
4d014124ac1d9ed6e002598ffdf56f21
500
Windbergs, Maike
847ca972abfd4354c696c146187cc604
500
2013-06-24T14:25:15Z
2013-06-24T14:25:15Z
2013-01
Freeze-drying as a preserving preparation technique for in vitro testing of human skin. 2013, 22 (1):54-6 Exp. Dermatol.
1600-0625
23278895
10.1111/exd.12058
http://hdl.handle.net/10033/294443
Experimental dermatology
In vitro testing of drugs with excised human skin is a valuable prerequisite for clinical studies. However, the analysis of excised human skin presents several obstacles. Ongoing drug diffusion, microbial growth and changes in hydration state influence the results of drug penetration studies. In this work, we evaluate freeze-drying as a preserving preparation method for skin samples to overcome these obstacles. We analyse excised human skin before and after freeze-drying and compare these results with human skin in vivo. Based on comprehensive thermal and spectroscopic analysis, we demonstrate comparability to in vivo conditions and exclude significant changes within the skin samples due to freeze-drying. Furthermore, we show that freeze-drying after skin incubation with drugs prevents growth of drug crystals on the skin surface due to drying effects. In conclusion, we introduce freeze-drying as a preserving preparation technique for in vitro testing of human skin.
en
Archived with thanks to Experimental dermatology
Freeze-drying as a preserving preparation technique for in vitro testing of human skin.
Article
2014-02-15T00:00:00Z
In vitro testing of drugs with excised human skin is a valuable prerequisite for clinical studies. However, the analysis of excised human skin presents several obstacles. Ongoing drug diffusion, microbial growth and changes in hydration state influence the results of drug penetration studies. In this work, we evaluate freeze-drying as a preserving preparation method for skin samples to overcome these obstacles. We analyse excised human skin before and after freeze-drying and compare these results with human skin in vivo. Based on comprehensive thermal and spectroscopic analysis, we demonstrate comparability to in vivo conditions and exclude significant changes within the skin samples due to freeze-drying. Furthermore, we show that freeze-drying after skin incubation with drugs prevents growth of drug crystals on the skin surface due to drying effects. In conclusion, we introduce freeze-drying as a preserving preparation technique for in vitro testing of human skin.
ORIGINAL
Frantzen et al_final.pdf
Frantzen et al_final.pdf
original manuscript
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10033/294443
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2019-08-30 11:33:30.098
Helmholtz Zentrum für Infektionsforschung Repository
hzi@openrepository.com
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oai:repository.helmholtz-hzi.de:10033/2959692019-08-30T11:33:29Zcom_10033_620613col_10033_620614
Kann, Birthe
44093398d479e26c1655831f6fa62bff
500
Windbergs, Maike
847ca972abfd4354c696c146187cc604
500
Department of Biopharmaceutics and Pharmaceutical Technology, Saarland University, Campus A4.1, 66123 Saarbruecken, Germany.
2013-07-15T09:59:52Z
2013-07-15T09:59:52Z
2013-04
Chemical imaging of drug delivery systems with structured surfaces-a combined analytical approach of confocal raman microscopy and optical profilometry. 2013, 15 (2):505-10 AAPS J
1550-7416
23358922
10.1208/s12248-013-9457-7
http://hdl.handle.net/10033/295969
The AAPS journal
Confocal Raman microscopy is an analytical technique with a steadily increasing impact in the field of pharmaceutics as the instrumental setup allows for nondestructive visualization of component distribution within drug delivery systems. Here, the attention is mainly focused on classic solid carrier systems like tablets, pellets, or extrudates. Due to the opacity of these systems, Raman analysis is restricted either to exterior surfaces or cross sections. As Raman spectra are only recorded from one focal plane at a time, the sample is usually altered to create a smooth and even surface. However, this manipulation can lead to misinterpretation of the analytical results. Here, we present a trendsetting approach to overcome these analytical pitfalls with a combination of confocal Raman microscopy and optical profilometry. By acquiring a topography profile of the sample area of interest prior to Raman spectroscopy, the profile height information allowed to level the focal plane to the sample surface for each spectrum acquisition. We first demonstrated the basic principle of this complementary approach in a case study using a tilted silica wafer. In a second step, we successfully adapted the two techniques to investigate an extrudate and a lyophilisate as two exemplary solid drug carrier systems. Component distribution analysis with the novel analytical approach was neither hampered by the curvature of the cylindrical extrudate nor the highly structured surface of the lyophilisate. Therefore, the combined analytical approach bears a great potential to be implemented in diversified fields of pharmaceutical sciences.
en
Archived with thanks to The AAPS journal
Chemical imaging of drug delivery systems with structured surfaces-a combined analytical approach of confocal raman microscopy and optical profilometry.
Article
2018-06-13T05:31:00Z
Confocal Raman microscopy is an analytical technique with a steadily increasing impact in the field of pharmaceutics as the instrumental setup allows for nondestructive visualization of component distribution within drug delivery systems. Here, the attention is mainly focused on classic solid carrier systems like tablets, pellets, or extrudates. Due to the opacity of these systems, Raman analysis is restricted either to exterior surfaces or cross sections. As Raman spectra are only recorded from one focal plane at a time, the sample is usually altered to create a smooth and even surface. However, this manipulation can lead to misinterpretation of the analytical results. Here, we present a trendsetting approach to overcome these analytical pitfalls with a combination of confocal Raman microscopy and optical profilometry. By acquiring a topography profile of the sample area of interest prior to Raman spectroscopy, the profile height information allowed to level the focal plane to the sample surface for each spectrum acquisition. We first demonstrated the basic principle of this complementary approach in a case study using a tilted silica wafer. In a second step, we successfully adapted the two techniques to investigate an extrudate and a lyophilisate as two exemplary solid drug carrier systems. Component distribution analysis with the novel analytical approach was neither hampered by the curvature of the cylindrical extrudate nor the highly structured surface of the lyophilisate. Therefore, the combined analytical approach bears a great potential to be implemented in diversified fields of pharmaceutical sciences.
ORIGINAL
Kann and Windbergs_final.pdf
Kann and Windbergs_final.pdf
original manuscript
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2019-08-30 11:33:29.987
Helmholtz Zentrum für Infektionsforschung Repository
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oai:repository.helmholtz-hzi.de:10033/2971112019-08-30T11:34:22Zcom_10033_620613col_10033_620614
Franzen, Lutz
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Selzer, Dominik
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Fluhr, Joachim W
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Schaefer, Ulrich F
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Windbergs, Maike
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Biopharmaceutics and Pharmaceutical Technology, Saarland University, Saarbruecken, Germany. lutz.franzen@mx.uni-saarland.de
2013-07-29T13:43:39Z
2013-07-29T13:43:39Z
2013-06
Towards drug quantification in human skin with confocal Raman microscopy. 2013, 84 (2):437-44 Eur J Pharm Biopharm
1873-3441
23220382
10.1016/j.ejpb.2012.11.017
http://hdl.handle.net/10033/297111
European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft für Pharmazeutische Verfahrenstechnik e.V
Understanding the penetration behaviour of drugs into human skin is a prerequisite for the rational development and evaluation of effective dermal drug delivery. The general procedure for the acquisition of quantitative drug penetration profiles in human skin is performed by sequential segmentation and extraction. Unfortunately, this technique is destructive, laborious and lacks spatial resolution. Confocal Raman microscopy bares the potential of a chemically selective, label free and nondestructive analysis. However, the acquisition of quantitative drug depth profiles within skin by Raman microscopy is impeded by imponderable signal attenuation inside the tissue. In this study, we present a chemical semi-solid matrix system simulating the optical properties of human skin. This system serves as a skin surrogate for investigation of Raman signal attenuation under controlled conditions. Caffeine was homogeneously incorporated within the skin surrogate, and Raman intensity depth profiles were acquired. A mathematical algorithm describing the Raman signal attenuation within the surrogate was derived from these profiles. Human skin samples were incubated with caffeine, and Raman intensity depth profiles were similarly acquired. The surrogate algorithm was successfully applied to correct the drug profiles in human skin for signal attenuation. For the first time, a mathematical algorithm was established, which allows correction of Raman signal attenuation in human skin, thus facilitating reliable drug quantification in human skin by confocal Raman spectroscopy.
en
Archived with thanks to European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft für Pharmazeutische Verfahrenstechnik e.V
Towards drug quantification in human skin with confocal Raman microscopy.
Article
2018-06-12T23:25:59Z
Understanding the penetration behaviour of drugs into human skin is a prerequisite for the rational development and evaluation of effective dermal drug delivery. The general procedure for the acquisition of quantitative drug penetration profiles in human skin is performed by sequential segmentation and extraction. Unfortunately, this technique is destructive, laborious and lacks spatial resolution. Confocal Raman microscopy bares the potential of a chemically selective, label free and nondestructive analysis. However, the acquisition of quantitative drug depth profiles within skin by Raman microscopy is impeded by imponderable signal attenuation inside the tissue. In this study, we present a chemical semi-solid matrix system simulating the optical properties of human skin. This system serves as a skin surrogate for investigation of Raman signal attenuation under controlled conditions. Caffeine was homogeneously incorporated within the skin surrogate, and Raman intensity depth profiles were acquired. A mathematical algorithm describing the Raman signal attenuation within the surrogate was derived from these profiles. Human skin samples were incubated with caffeine, and Raman intensity depth profiles were similarly acquired. The surrogate algorithm was successfully applied to correct the drug profiles in human skin for signal attenuation. For the first time, a mathematical algorithm was established, which allows correction of Raman signal attenuation in human skin, thus facilitating reliable drug quantification in human skin by confocal Raman spectroscopy.
ORIGINAL
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Helmholtz Zentrum für Infektionsforschung Repository
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oai:repository.helmholtz-hzi.de:10033/2972092019-08-30T11:34:22Zcom_10033_620613col_10033_620614
Schneider, Marc
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Windbergs, Maike
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Daum, Nicole
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Loretz, Brigitta
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Collnot, Eva-Maria
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Hansen, Steffi
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Schaefer, Ulrich F
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Lehr, Claus-Michael
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2013-08-01T12:48:17Z
2013-08-01T12:48:17Z
2013-06
Crossing biological barriers for advanced drug delivery. 2013, 84 (2):239-41 Eur J Pharm Biopharm
1873-3441
23531604
10.1016/j.ejpb.2013.03.009
http://hdl.handle.net/10033/297209
European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft für Pharmazeutische Verfahrenstechnik e.V
This special issue compiles invited and contributed papers of the 9th International Conference and Workshop "Biological Barriers", 29 February-9 March 2012 at Saarland University, Saarbrücken Germany.
en
Archived with thanks to European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft für Pharmazeutische Verfahrenstechnik e.V
Crossing biological barriers for advanced drug delivery.
Article
2018-06-13T05:23:10Z
This special issue compiles invited and contributed papers of the 9th International Conference and Workshop "Biological Barriers", 29 February-9 March 2012 at Saarland University, Saarbrücken Germany.
ORIGINAL
Schneider et al_final.pdf
Schneider et al_final.pdf
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Helmholtz Zentrum für Infektionsforschung Repository
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Thude, Sibylle
17dcacdbbad1cf9bddbacd8ca104b6cc
500
Schneider, Marc
43297aa0fabdc7552ad4154ab037617a
500
Helmholtz Center for Infection Research, Helmholtz Institute for Pharmaceutical Research Saarland, Saarbrücken, Germany.
2013-08-06T09:20:32Z
2013-08-06T09:20:32Z
2013-06
Setup for investigating gold nanoparticle penetration through reconstructed skin and comparison to published human skin data. 2013, 18 (6):061218 J Biomed Opt
1560-2281
23203297
10.1117/1.JBO.18.6.061218
http://hdl.handle.net/10033/297445
Journal of biomedical optics
Owing to the limited source of human skin (HS) and the ethical restrictions of using animals in experiments, in vitro skin equivalents are a possible alternative for conducting particle penetration experiments. The conditions for conducting penetration experiments with model particles, 15-nm gold nanoparticles (AuNP), through nonsealed skin equivalents are described for the first time. These conditions include experimental setup, sterility conditions, effective applied dose determination, skin sectioning, and skin integrity check. Penetration at different exposure times (two and 24 h) and after tissue fixation (fixed versus unfixed skin) are examined to establish a benchmark in comparison to HS in an attempt to get similar results to HS experiments presented earlier. Multiphoton microscopy is used to detect gold luminescence in skin sections. λ(ex)=800 nm is used for excitation of AuNP and skin samples, allowing us to determine a relative index for particle penetration. Despite the observed overpredictability of penetration into skin equivalents, they could serve as a first fast screen for testing the behavior of nanoparticles and extrapolate their penetration behavior into HS. Further investigations are required to test a wide range of particles of different physicochemical properties to validate the skin equivalent-human skin particle penetration relationship.
en
Archived with thanks to Journal of biomedical optics
Biomedical Research
Cell Culture Techniques
Cells, Cultured
Fibroblasts
Gold
Humans
Keratinocytes
Metal Nanoparticles
Microscopy, Fluorescence, Multiphoton
Models, Biological
Permeability
Reproducibility of Results
Skin
Setup for investigating gold nanoparticle penetration through reconstructed skin and comparison to published human skin data.
Article
2018-06-13T04:22:44Z
Owing to the limited source of human skin (HS) and the ethical restrictions of using animals in experiments, in vitro skin equivalents are a possible alternative for conducting particle penetration experiments. The conditions for conducting penetration experiments with model particles, 15-nm gold nanoparticles (AuNP), through nonsealed skin equivalents are described for the first time. These conditions include experimental setup, sterility conditions, effective applied dose determination, skin sectioning, and skin integrity check. Penetration at different exposure times (two and 24 h) and after tissue fixation (fixed versus unfixed skin) are examined to establish a benchmark in comparison to HS in an attempt to get similar results to HS experiments presented earlier. Multiphoton microscopy is used to detect gold luminescence in skin sections. λ(ex)=800 nm is used for excitation of AuNP and skin samples, allowing us to determine a relative index for particle penetration. Despite the observed overpredictability of penetration into skin equivalents, they could serve as a first fast screen for testing the behavior of nanoparticles and extrapolate their penetration behavior into HS. Further investigations are required to test a wide range of particles of different physicochemical properties to validate the skin equivalent-human skin particle penetration relationship.
ORIGINAL
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2019-08-30 11:33:05.437
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oai:repository.helmholtz-hzi.de:10033/3019992019-08-30T11:34:19Zcom_10033_620613col_10033_620614
Ali, Hussain
3ff577f359fa64697d95940bd8f4e92b
500
Collnot, Eva-Maria
d50b143a6afb06ea170774022703c458
500
Windbergs, Maike
847ca972abfd4354c696c146187cc604
500
Lehr, Claus-Michael
e25b30ba80302580419199334c0f4c6b
500
2013-09-20T13:26:56Z
2013-09-20T13:26:56Z
2013-09-20
Nanomedicines for the treatment of inflammatory bowel diseases 2013, 5 (1) European Journal of Nanomedicine
1662-596X
1662-5986
10.1515/ejnm-2013-0004
http://hdl.handle.net/10033/301999
European Journal of Nanomedicine
http://www.degruyter.com/view/j/ejnm.2013.5.issue-1/ejnm-2013-0004/ejnm-2013-0004.xml
Archived with thanks to European Journal of Nanomedicine
Nanomedicines for the treatment of inflammatory bowel diseases
Article
2014-08-15T00:00:00Z
ORIGINAL
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2019-08-30 11:34:19.067
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oai:repository.helmholtz-hzi.de:10033/3057212019-08-30T11:27:46Zcom_10033_620613col_10033_620614
Mittal, Ankit
129a97a9dbee220b00f051772b15839a
500
Raber, Anne S
b979f0824847e52f24ba5196eb3916ec
500
Hansen, Steffi
6bb9ae2a7d6ae348419e78349d92c93f
500
Biopharmaceutics and Pharmaceutical Technology; Saarland University; Saarbruecken, Germany.
2013-11-25T10:00:20Z
2013-11-25T10:00:20Z
2013-06-18
Particle based vaccine formulations for transcutaneous immunization. 2013, 9 (9): Hum Vaccin Immunother
2164-554X
23778884
http://hdl.handle.net/10033/305721
Human vaccines & immunotherapeutics
Vaccine formulations on the basis of nano- (NP) or microparticles (MP) can solve issues with stabilization, controlled release, and poor immunogenicity of antigens. Likewise transcutaneous immunization (TCI) promises superior immunogenicity as well as the advantages of needle-free application compared with conventional intramuscular injections. Thus the combination of both strategies seems to be a very valuable approach. However, until now TCI using particle based vaccine formulations has made no impact on medical practice. One of the main difficulties is that NPs and MPs cannot penetrate the skin to an extent that would allow the application of the required dose of antigen. This is due to the formidable stratum corneum (SC) barrier, the limited amount of antigen in the formulation and often an insufficient immunogenicity. A multitude of strategies are currently under investigation to overcome these issues. We highlight selected methods presenting a spectrum of solutions ranging from transfollicular delivery, to devices disrupting the SC barrier and the combination of particle based vaccines with adjuvants discussing their advantages and shortcomings. Some of these are currently at an experimental state while others are already in clinical testing. All methods have been shown to be capable of transcutaneous antigen delivery.
ENG
Archived with thanks to Human vaccines & immunotherapeutics
Particle based vaccine formulations for transcutaneous immunization.
Article
2018-06-12T22:16:02Z
Vaccine formulations on the basis of nano- (NP) or microparticles (MP) can solve issues with stabilization, controlled release, and poor immunogenicity of antigens. Likewise transcutaneous immunization (TCI) promises superior immunogenicity as well as the advantages of needle-free application compared with conventional intramuscular injections. Thus the combination of both strategies seems to be a very valuable approach. However, until now TCI using particle based vaccine formulations has made no impact on medical practice. One of the main difficulties is that NPs and MPs cannot penetrate the skin to an extent that would allow the application of the required dose of antigen. This is due to the formidable stratum corneum (SC) barrier, the limited amount of antigen in the formulation and often an insufficient immunogenicity. A multitude of strategies are currently under investigation to overcome these issues. We highlight selected methods presenting a spectrum of solutions ranging from transfollicular delivery, to devices disrupting the SC barrier and the combination of particle based vaccines with adjuvants discussing their advantages and shortcomings. Some of these are currently at an experimental state while others are already in clinical testing. All methods have been shown to be capable of transcutaneous antigen delivery.
ORIGINAL
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Helmholtz Zentrum für Infektionsforschung Repository
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oai:repository.helmholtz-hzi.de:10033/3067012019-08-30T11:35:39Zcom_10033_620613col_10033_620614
Schrank, Simone
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Kann, Birthe
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Windbergs, Maike
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Glasser, Benjamin J
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Zimmer, Andreas
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Khinast, Johannes
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Roblegg, Eva
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Institute for Process and Particle Engineering, Graz University of Technology, Graz, Austria; Research Center Pharmaceutical Engineering GmbH, Graz, Austria; Institute of Pharmaceutical Sciences, Department of Pharmaceutical Technology, University of Graz, Graz, Austria.
2013-12-11T08:40:59Z
2013-12-11T08:40:59Z
2013-11
Microstructure of calcium stearate matrix pellets: a function of the drying process. 2013, 102 (11):3987-97 J Pharm Sci
1520-6017
23983150
10.1002/jps.23707
http://hdl.handle.net/10033/306701
Journal of pharmaceutical sciences
Drying is a common pharmaceutical process, whose potential to modify the final drug and/or dosage form properties is often underestimated. In the present study, pellets consisting of the matrix former calcium stearate (CaSt) incorporating the active pharmaceutical ingredient ibuprofen were prepared via wet extrusion and spheronization. Subsequent drying was performed by either desiccation, fluid-bed drying, or lyophilization, and the final pellets were compared with respect to their microstructure. To minimize the effect of solute ibuprofen molecules on the shrinking behavior of the CaSt, low ibuprofen loadings were used, as ibuprofen is soluble in the granulation liquid. Pellet porosity and specific surface area increased during desiccation, fluid-bed drying, and lyophilization. The inlet-air temperature during fluid-bed drying affected the specific surface area, which increased at lower inlet-air temperatures rather than the pellet porosity. The in vitro dissolution profiles were found to be a nonlinear function of the specific surface area. Overall, the microstructure, including porosity, pore size, and specific surface area, of CaSt pellets was a strong function of the drying conditions.
en
Archived with thanks to Journal of pharmaceutical sciences
Microstructure of calcium stearate matrix pellets: a function of the drying process.
Article
2018-06-12T17:42:11Z
Drying is a common pharmaceutical process, whose potential to modify the final drug and/or dosage form properties is often underestimated. In the present study, pellets consisting of the matrix former calcium stearate (CaSt) incorporating the active pharmaceutical ingredient ibuprofen were prepared via wet extrusion and spheronization. Subsequent drying was performed by either desiccation, fluid-bed drying, or lyophilization, and the final pellets were compared with respect to their microstructure. To minimize the effect of solute ibuprofen molecules on the shrinking behavior of the CaSt, low ibuprofen loadings were used, as ibuprofen is soluble in the granulation liquid. Pellet porosity and specific surface area increased during desiccation, fluid-bed drying, and lyophilization. The inlet-air temperature during fluid-bed drying affected the specific surface area, which increased at lower inlet-air temperatures rather than the pellet porosity. The in vitro dissolution profiles were found to be a nonlinear function of the specific surface area. Overall, the microstructure, including porosity, pore size, and specific surface area, of CaSt pellets was a strong function of the drying conditions.
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oai:hzi.openrepository.com:10033/306701
2019-08-30 11:35:39.754
Helmholtz Zentrum für Infektionsforschung Repository
hzi@openrepository.com
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oai:repository.helmholtz-hzi.de:10033/3207932019-08-30T11:37:00Zcom_10033_620613col_10033_620614
Kirch, Julian
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Schneider, Andreas
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Abou, Bérengère
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Hopf, Alexander
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Schaefer, Ulrich F
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Schneider, Marc
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Schall, Christian
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Wagner, Christian
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Lehr, Claus-Michael
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2014-06-11T12:57:10Z
2014-06-11T12:57:10Z
2012-11-06
Optical tweezers reveal relationship between microstructure and nanoparticle penetration of pulmonary mucus. 2012, 109 (45):18355-60 Proc. Natl. Acad. Sci. U.S.A.
1091-6490
23091027
10.1073/pnas.1214066109
http://hdl.handle.net/10033/320793
Proceedings of the National Academy of Sciences of the United States of America
In this study, the mobility of nanoparticles in mucus and similar hydrogels as model systems was assessed to elucidate the link between microscopic diffusion behavior and macroscopic penetration of such gels. Differences in particle adhesion to mucus components were strongly dependent on particle coating. Particles coated with 2 kDa PEG exhibited a decreased adhesion to mucus components, whereas chitosan strongly increased the adhesion. Despite such mucoinert properties of PEG, magnetic nanoparticles of both coatings did not penetrate through native respiratory mucus, resisting high magnetic forces (even for several hours). However, model hydrogels were, indeed, penetrated by both particles in dependency of particle coating, obeying the theory of particle mobility in an external force field. Comparison of penetration data with cryogenic scanning EM images of mucus and the applied model systems suggested particularly high rigidity of the mucin scaffold and a broad pore size distribution in mucus as reasons for the observed particle immobilization. Active probing of the rigidity of mucus and model gels with optical tweezers was used in this context to confirm such properties of mucus on the microscale, thus presenting the missing link between micro- and macroscopical observations. Because of high heterogeneity in the size of the voids and pores in mucus, on small scales, particle mobility will depend on adhesive or inert properties. However, particle translocation over distances larger than a few micrometers is restricted by highly rigid structures within the mucus mesh.
en
Archived with thanks to Proceedings of the National Academy of Sciences of the United States of America
Cellulose
Cryoelectron Microscopy
Humans
Hydrogels
Lung
Magnetic Phenomena
Microscopy, Atomic Force
Mucus
Nanoparticles
Optical Tweezers
Particle Size
Polyethylene Glycols
Rheology
Optical tweezers reveal relationship between microstructure and nanoparticle penetration of pulmonary mucus.
Article
2018-06-13T21:29:12Z
In this study, the mobility of nanoparticles in mucus and similar hydrogels as model systems was assessed to elucidate the link between microscopic diffusion behavior and macroscopic penetration of such gels. Differences in particle adhesion to mucus components were strongly dependent on particle coating. Particles coated with 2 kDa PEG exhibited a decreased adhesion to mucus components, whereas chitosan strongly increased the adhesion. Despite such mucoinert properties of PEG, magnetic nanoparticles of both coatings did not penetrate through native respiratory mucus, resisting high magnetic forces (even for several hours). However, model hydrogels were, indeed, penetrated by both particles in dependency of particle coating, obeying the theory of particle mobility in an external force field. Comparison of penetration data with cryogenic scanning EM images of mucus and the applied model systems suggested particularly high rigidity of the mucin scaffold and a broad pore size distribution in mucus as reasons for the observed particle immobilization. Active probing of the rigidity of mucus and model gels with optical tweezers was used in this context to confirm such properties of mucus on the microscale, thus presenting the missing link between micro- and macroscopical observations. Because of high heterogeneity in the size of the voids and pores in mucus, on small scales, particle mobility will depend on adhesive or inert properties. However, particle translocation over distances larger than a few micrometers is restricted by highly rigid structures within the mucus mesh.
ORIGINAL
Kirch et al_final.pdf
Kirch et al_final.pdf
copy from PubMed Centrals' repository
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In vitro toxicological screening of nanoparticles on primary human endothelial cells and the role of flow in modulating cell response. 2014, 8 (6):697-708 Nanotoxicology
1743-5404
23909703
10.3109/17435390.2013.831500
http://hdl.handle.net/10033/323907
Nanotoxicology
After passage through biological barriers, nanomaterials inevitably end up in contact with the vascular endothelium and can induce cardiovascular damage. In this study the toxicity and sub-lethal effects of six types of nanoparticle, including four of industrial and biomedical importance, on human endothelial cells were investigated using different in vitro assays. The results show that all the particles investigated induce some level of damage to the cells and that silver particles were most toxic, followed by titanium dioxide. Furthermore, endothelial cells were shown to be more susceptible when exposed to silver nanoparticles under flow conditions in a bioreactor. The study underlines that although simple in vitro tests are useful to screen compounds and to identify the type of effect induced on cells, they may not be sufficient to define safe exposure limits. Therefore, once initial toxicity screening has been conducted on nanomaterials, it is necessary to develop more physiologically relevant in vitro models to better understand how nanomaterials can impact on human health.
en
Archived with thanks to Nanotoxicology
Apoptosis
Cell Survival
Cells, Cultured
Cytokines
Dose-Response Relationship, Drug
Human Umbilical Vein Endothelial Cells
Humans
Nanoparticles
Polystyrenes
Silver
Titanium
von Willebrand Factor
In vitro toxicological screening of nanoparticles on primary human endothelial cells and the role of flow in modulating cell response.
Article
2015-07-15T00:00:00Z
After passage through biological barriers, nanomaterials inevitably end up in contact with the vascular endothelium and can induce cardiovascular damage. In this study the toxicity and sub-lethal effects of six types of nanoparticle, including four of industrial and biomedical importance, on human endothelial cells were investigated using different in vitro assays. The results show that all the particles investigated induce some level of damage to the cells and that silver particles were most toxic, followed by titanium dioxide. Furthermore, endothelial cells were shown to be more susceptible when exposed to silver nanoparticles under flow conditions in a bioreactor. The study underlines that although simple in vitro tests are useful to screen compounds and to identify the type of effect induced on cells, they may not be sufficient to define safe exposure limits. Therefore, once initial toxicity screening has been conducted on nanomaterials, it is necessary to develop more physiologically relevant in vitro models to better understand how nanomaterials can impact on human health.
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Antibiotic-free nanotherapeutics: Ultra-small, mucus-penetrating solid lipid nanoparticles enhance the pulmonary delivery and anti-virulence efficacy of novel quorum sensing inhibitors. 2014, 192:131-40 J Control Release
1873-4995
24997276
10.1016/j.jconrel.2014.06.055
http://hdl.handle.net/10033/332860
Journal of controlled release : official journal of the Controlled Release Society
Cystic fibrosis (CF) is a genetic disease mainly manifested in the respiratory tract. Pseudomonas aeruginosa (P. aeruginosa) is the most common pathogen identified in cultures of the CF airways, however, its eradication with antibiotics remains challenging as it grows in biofilms that counterwork human immune response and dramatically decrease susceptibility to antibiotics. P. aeruginosa regulates pathogenicity via a cell-to-cell communication system known as quorum sensing (QS) involving the virulence factor (pyocyanin), thus representing an attractive target for coping with bacterial pathogenicity. The first in vivo potent QS inhibitor (QSI) was recently developed. Nevertheless, its lipophilic nature might hamper its penetration of non-cellular barriers such as mucus and bacterial biofilms, which limits its biomedical application. Successful anti-infective inhalation therapy necessitates proper design of a biodegradable nanocarrier allowing: 1) high loading and prolonged release, 2) mucus penetration, 3) effective pulmonary delivery, and 4) maintenance of the anti-virulence activity of the QSI. In this context, various pharmaceutical lipids were used to prepare ultra-small solid lipid nanoparticles (us-SLNs) by hot melt homogenization. Plain and QSI-loaded SLNs were characterized in terms of colloidal properties, drug loading, in vitro release and acute toxicity on Calu-3 cells. Mucus penetration was studied using a newly-developed confocal microscopy technique based on 3D-time-lapse imaging. For pulmonary application, nebulization efficiency of SLNs and lung deposition using next generation impactor (NGI) were performed. The anti-virulence efficacy was investigated by pyocyanin formation in P. aeruginosa cultures. Ultra-small SLNs (<100nm diameter) provided high encapsulation efficiency (68-95%) according to SLN composition, high burst in phosphate buffer saline compared to prolonged release of the payload over >8h in simulated lung fluid with minor burst. All types and concentrations of plain and QSI-loaded SLNs maintained the viability of Calu-3 cells. 3D time-lapse confocal imaging proved the ability of SLNs to penetrate into artificial sputum model. SLNs were efficiently nebulized; NGI experiments revealed their deposition in the bronchial region. Overall, nanoencapsulated QSI showed up to sevenfold superior anti-virulence activity to the free compound. Most interestingly, the plain SLNs exhibited anti-virulence properties themselves, which was shown to be related to anti-virulence effects of the emulsifiers used. These startling findings represent a new perspective of ultimate significance in the area of nano-based delivery of novel anti-infectives.
en
Archived with thanks to Journal of controlled release : official journal of the Controlled Release Society
Antibiotic-free nanotherapeutics: Ultra-small, mucus-penetrating solid lipid nanoparticles enhance the pulmonary delivery and anti-virulence efficacy of novel quorum sensing inhibitors.
Article
2018-06-12T21:28:50Z
Cystic fibrosis (CF) is a genetic disease mainly manifested in the respiratory tract. Pseudomonas aeruginosa (P. aeruginosa) is the most common pathogen identified in cultures of the CF airways, however, its eradication with antibiotics remains challenging as it grows in biofilms that counterwork human immune response and dramatically decrease susceptibility to antibiotics. P. aeruginosa regulates pathogenicity via a cell-to-cell communication system known as quorum sensing (QS) involving the virulence factor (pyocyanin), thus representing an attractive target for coping with bacterial pathogenicity. The first in vivo potent QS inhibitor (QSI) was recently developed. Nevertheless, its lipophilic nature might hamper its penetration of non-cellular barriers such as mucus and bacterial biofilms, which limits its biomedical application. Successful anti-infective inhalation therapy necessitates proper design of a biodegradable nanocarrier allowing: 1) high loading and prolonged release, 2) mucus penetration, 3) effective pulmonary delivery, and 4) maintenance of the anti-virulence activity of the QSI. In this context, various pharmaceutical lipids were used to prepare ultra-small solid lipid nanoparticles (us-SLNs) by hot melt homogenization. Plain and QSI-loaded SLNs were characterized in terms of colloidal properties, drug loading, in vitro release and acute toxicity on Calu-3 cells. Mucus penetration was studied using a newly-developed confocal microscopy technique based on 3D-time-lapse imaging. For pulmonary application, nebulization efficiency of SLNs and lung deposition using next generation impactor (NGI) were performed. The anti-virulence efficacy was investigated by pyocyanin formation in P. aeruginosa cultures. Ultra-small SLNs (<100nm diameter) provided high encapsulation efficiency (68-95%) according to SLN composition, high burst in phosphate buffer saline compared to prolonged release of the payload over >8h in simulated lung fluid with minor burst. All types and concentrations of plain and QSI-loaded SLNs maintained the viability of Calu-3 cells. 3D time-lapse confocal imaging proved the ability of SLNs to penetrate into artificial sputum model. SLNs were efficiently nebulized; NGI experiments revealed their deposition in the bronchial region. Overall, nanoencapsulated QSI showed up to sevenfold superior anti-virulence activity to the free compound. Most interestingly, the plain SLNs exhibited anti-virulence properties themselves, which was shown to be related to anti-virulence effects of the emulsifiers used. These startling findings represent a new perspective of ultimate significance in the area of nano-based delivery of novel anti-infectives.
ORIGINAL
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Helmholtz Zentrum für Infektionsforschung Repository
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oai:repository.helmholtz-hzi.de:10033/3378492019-08-30T11:34:48Zcom_10033_620613col_10033_620614
Nnamani, Petra O
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Hansen, Steffi
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Windbergs, Maike
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Lehr, Claus-Michael
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2015-01-05T15:52:09Z
2015-01-05T15:52:09Z
2014-12-30
Development of artemether-loaded nanostructured lipid carrier (NLC) formulation for topical application. 2014, 477 (1-2):208-17 Int J Pharm
1873-3476
25290810
10.1016/j.ijpharm.2014.10.004
http://hdl.handle.net/10033/337849
International journal of pharmaceutics
NLC topical formulation as an alternative to oral and parenteral (IM) delivery of artemether (ART), a poorly water-soluble drug was designed. A Phospholipon 85G-modified Gelucire 43/01 based NLC formulation containing 75% Transcutol was chosen from DSC studies and loaded with gradient concentration of ART (100-750mg). ART-loaded NLCs were stable (-22 to -40mV), polydispersed (0.4-0.7) with d90 size distribution range of 247-530nm without microparticles up to one month of storage. The encapsulation efficiency (EE%) for ART in the NLC was concentration independent as 250mg of ART loading achieved ∼61%. DSC confirmed molecular dispersion of ART due to low matrix crystallinity (0.028J/g). Ex vivo study showed detectable ART amounts after 20h which gradually increased over 48h achieving ∼26% cumulative amount permeated irrespective of the applied dose. This proves that ART permeates excised human epidermis, where the current formulation served as a reservoir to gradually control drug release over an extended period of time. Full thickness skin study therefore may confirm if this is a positive signal to hope for a topical delivery system of ART.
en
Development of artemether-loaded nanostructured lipid carrier (NLC) formulation for topical application.
Article
2018-06-13T07:46:29Z
NLC topical formulation as an alternative to oral and parenteral (IM) delivery of artemether (ART), a poorly water-soluble drug was designed. A Phospholipon 85G-modified Gelucire 43/01 based NLC formulation containing 75% Transcutol was chosen from DSC studies and loaded with gradient concentration of ART (100-750mg). ART-loaded NLCs were stable (-22 to -40mV), polydispersed (0.4-0.7) with d90 size distribution range of 247-530nm without microparticles up to one month of storage. The encapsulation efficiency (EE%) for ART in the NLC was concentration independent as 250mg of ART loading achieved ∼61%. DSC confirmed molecular dispersion of ART due to low matrix crystallinity (0.028J/g). Ex vivo study showed detectable ART amounts after 20h which gradually increased over 48h achieving ∼26% cumulative amount permeated irrespective of the applied dose. This proves that ART permeates excised human epidermis, where the current formulation served as a reservoir to gradually control drug release over an extended period of time. Full thickness skin study therefore may confirm if this is a positive signal to hope for a topical delivery system of ART.
ORIGINAL
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TEXT
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THUMBNAIL
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10033/337849
oai:hzi.openrepository.com:10033/337849
2019-08-30 11:34:48.479
Helmholtz Zentrum für Infektionsforschung Repository
hzi@openrepository.com
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oai:repository.helmholtz-hzi.de:10033/3386612019-08-30T11:36:33Zcom_10033_620613col_10033_620614
Goikoetxea, Estibalitz
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Murgia, Xabier
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Serna-Grande, Pablo
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Valls-i-Soler, Adolf
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Rey-Santano, Carmen
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Rivas, Alejandro
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Antón, Raúl
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Basterretxea, Francisco J
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Miñambres, Lorena
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Méndez, Estíbaliz
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Lopez-Arraiza, Alberto
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Larrabe-Barrena, Juan Luis
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Gomez-Solaetxe, Miguel Angel
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2015-01-22T10:46:25Z
2015-01-22T10:46:25Z
2014
In vitro surfactant and perfluorocarbon aerosol deposition in a neonatal physical model of the upper conducting airways. 2014, 9 (9):e106835 PLoS ONE
1932-6203
25211475
10.1371/journal.pone.0106835
http://hdl.handle.net/10033/338661
PloS one
Aerosol delivery holds potential to release surfactant or perfluorocarbon (PFC) to the lungs of neonates with respiratory distress syndrome with minimal airway manipulation. Nevertheless, lung deposition in neonates tends to be very low due to extremely low lung volumes, narrow airways and high respiratory rates. In the present study, the feasibility of enhancing lung deposition by intracorporeal delivery of aerosols was investigated using a physical model of neonatal conducting airways.
en
In vitro surfactant and perfluorocarbon aerosol deposition in a neonatal physical model of the upper conducting airways.
Article
2018-06-12T21:39:34Z
Aerosol delivery holds potential to release surfactant or perfluorocarbon (PFC) to the lungs of neonates with respiratory distress syndrome with minimal airway manipulation. Nevertheless, lung deposition in neonates tends to be very low due to extremely low lung volumes, narrow airways and high respiratory rates. In the present study, the feasibility of enhancing lung deposition by intracorporeal delivery of aerosols was investigated using a physical model of neonatal conducting airways.
LICENSE
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ORIGINAL
Goikoetxea et al_final.pdf
Goikoetxea et al_final.pdf
Open Access puplication
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TEXT
Goikoetxea et al_final.pdf.txt
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THUMBNAIL
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10033/338661
oai:hzi.openrepository.com:10033/338661
2019-08-30 11:36:33.011
Helmholtz Zentrum für Infektionsforschung Repository
hzi@openrepository.com
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oai:repository.helmholtz-hzi.de:10033/5563682019-08-30T11:31:18Zcom_10033_620613col_10033_620614
Jain, Ratnesh
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Dandekar, Prajakta
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Loretz, Brigitta
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Lehr, Claus-Michael
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elmholtz-Institute for Pharmaceutical Research Saarland (HIPS), Campus A4 1, Saarland University, Saarbrücken, 66123 Germany.
2015-06-04T11:53:42Z
2015-06-04T11:53:42Z
2015
Dimethylaminoethyl methacrylate copolymer-siRNA nanoparticles for silencing a therapeutically relevant gene in macrophages 2015, 6 (4):691 Med. Chem. Commun.
2040-2503
2040-2511
10.1039/C4MD00490F
http://hdl.handle.net/10033/556368
Med. Chem. Commun.
http://xlink.rsc.org/?DOI=C4MD00490F
Dimethylaminoethyl methacrylate copolymer-siRNA nanoparticles for silencing a therapeutically relevant gene in macrophages
Article
2018-06-13T19:46:45Z
ORIGINAL
Jain et al_final.pdf
Jain et al_final.pdf
Open Access article
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MD5
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CC-LICENSE
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MD5
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license_text
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MD5
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license_rdf
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LICENSE
license.txt
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MD5
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TEXT
Jain et al_final.pdf.txt
Jain et al_final.pdf.txt
Extracted Text
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MD5
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THUMBNAIL
Jain et al_final.pdf.jpg
Jain et al_final.pdf.jpg
Generated Thumbnail
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10033/556368
oai:hzi.openrepository.com:10033/556368
2019-08-30 11:31:18.904
Helmholtz Zentrum für Infektionsforschung Repository
hzi@openrepository.com
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oai:repository.helmholtz-hzi.de:10033/5662642019-08-30T11:32:13Zcom_10033_620613col_10033_620614
Mahiny, Azita J
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Dewerth, Alexander
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Alkhaled, Mohammed
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Mothes, Benedikt
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Loretz, Brigitta
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Rottenberger, Jennifer
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Surapolchai, Pacharapan
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Carevic, Melanie
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Griese, Matthias
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Schwab, Matthias
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Nürnberg, Bernd
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Beer-Hammer, Sandra
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Handgretinger, Rupert
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Hartl, Dominik
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Lehr, Claus-Michael
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Kormann, Michael S D
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Helmholtz Institute for Pharmaceutical Research Saarland (HIPS)
2015-08-13T08:18:55Z
2015-08-13T08:18:55Z
2015-06
In vivo genome editing using nuclease-encoding mRNA corrects SP-B deficiency. 2015, 33 (6):584-6 Nat. Biotechnol.
1546-1696
25985262
10.1038/nbt.3241
http://hdl.handle.net/10033/566264
Nature biotechnology
en
In vivo genome editing using nuclease-encoding mRNA corrects SP-B deficiency.
Article
2015-12-15T00:00:00Z
ORIGINAL
Mahiny et al_final.pdf
Mahiny et al_final.pdf
original manuscript
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MD5
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Figure 1.jpg
Figure 1.jpg
figure 1
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Figure 2.jpg
Figure 2.jpg
figure 2
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NBT-TR34055E Supplementary Materials.pdf
NBT-TR34055E Supplementary Materials.pdf
supplemental materials
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CC-LICENSE
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license_rdf
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LICENSE
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MD5
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TEXT
Mahiny et al_final.pdf.txt
Mahiny et al_final.pdf.txt
Extracted Text
text/plain
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https://hzi.openrepository.com/bitstream/10033/566264/15/Mahiny%20et%20al_final.pdf.txt
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MD5
15
false
NBT-TR34055E Supplementary Materials.pdf.txt
NBT-TR34055E Supplementary Materials.pdf.txt
Extracted Text
text/plain
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https://hzi.openrepository.com/bitstream/10033/566264/16/NBT-TR34055E%20Supplementary%20Materials.pdf.txt
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MD5
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false
THUMBNAIL
Figure 1.jpg.jpg
Figure 1.jpg.jpg
Generated Thumbnail
image/jpeg
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https://hzi.openrepository.com/bitstream/10033/566264/18/Figure%201.jpg.jpg
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MD5
18
false
Figure 2.jpg.jpg
Figure 2.jpg.jpg
Generated Thumbnail
image/jpeg
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https://hzi.openrepository.com/bitstream/10033/566264/19/Figure%202.jpg.jpg
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MD5
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Mahiny et al_final.pdf.jpg
Mahiny et al_final.pdf.jpg
Generated Thumbnail
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MD5
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NBT-TR34055E Supplementary Materials.pdf.jpg
NBT-TR34055E Supplementary Materials.pdf.jpg
Generated Thumbnail
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10033/566264
oai:hzi.openrepository.com:10033/566264
2019-08-30 11:32:13.184
Helmholtz Zentrum für Infektionsforschung Repository
hzi@openrepository.com
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oai:repository.helmholtz-hzi.de:10033/5765882019-08-30T11:28:24Zcom_10033_620613col_10033_620614
Nielsen, Line Hagner
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Nagstrup, Johan
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Gordon, Sarah
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Keller, Stephan Sylvest
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Østergaard, Jesper
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Rades, Thomas
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Müllertz, Anette
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Boisen, Anja
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2015-09-03T13:58:39Z
2015-09-03T13:58:39Z
2015-06
pH-triggered drug release from biodegradable microwells for oral drug delivery. 2015, 17 (3):9958 Biomed Microdevices
1572-8781
25981751
10.1007/s10544-015-9958-5
http://hdl.handle.net/10033/576588
Biomedical microdevices
Microwells fabricated from poly-L-lactic acid (PLLA) were evaluated for their application as an oral drug delivery system using the amorphous sodium salt of furosemide (ASSF) as a model drug. Hot embossing of PLLA resulted in fabrication of microwells with an inner diameter of 240 μm and a height of 100 μm. The microwells were filled with ASSF using a modified screen printing technique, followed by coating of the microwell cavities with a gastro-resistant lid of Eudragit® L100. The release behavior of ASSF from the coated microwells was investigated using a μ-Diss profiler and a UV imaging system, and under conditions simulating the changing environment of the gastrointestinal tract. Biorelevant gastric medium (pH 1.6) was employed, after which a change to biorelevant intestinal release medium (pH 6.5) was carried out. Both μ-Diss profiler and UV imaging release experiments showed that sealing of microwell cavities with an Eudragit® layer prevented drug release in biorelevant gastric medium. An immediate release of the ASSF from coated microwells was observed in the intestinal medium. This pH-triggered release behavior demonstrates the future potential of PLLA microwells as a site-specific oral drug delivery system.
en
pH-triggered drug release from biodegradable microwells for oral drug delivery.
Article
2016-06-15T00:00:00Z
Microwells fabricated from poly-L-lactic acid (PLLA) were evaluated for their application as an oral drug delivery system using the amorphous sodium salt of furosemide (ASSF) as a model drug. Hot embossing of PLLA resulted in fabrication of microwells with an inner diameter of 240 μm and a height of 100 μm. The microwells were filled with ASSF using a modified screen printing technique, followed by coating of the microwell cavities with a gastro-resistant lid of Eudragit® L100. The release behavior of ASSF from the coated microwells was investigated using a μ-Diss profiler and a UV imaging system, and under conditions simulating the changing environment of the gastrointestinal tract. Biorelevant gastric medium (pH 1.6) was employed, after which a change to biorelevant intestinal release medium (pH 6.5) was carried out. Both μ-Diss profiler and UV imaging release experiments showed that sealing of microwell cavities with an Eudragit® layer prevented drug release in biorelevant gastric medium. An immediate release of the ASSF from coated microwells was observed in the intestinal medium. This pH-triggered release behavior demonstrates the future potential of PLLA microwells as a site-specific oral drug delivery system.
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2019-08-30 11:28:24.104
Helmholtz Zentrum für Infektionsforschung Repository
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oai:repository.helmholtz-hzi.de:10033/5770162019-08-30T11:36:32Zcom_10033_620613col_10033_620614
Rietscher, René
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500
Thum, Carolin
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Lehr, Claus-Michael
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Schneider, Marc
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Helmholtz Institute for Pharmaceutical Research Saarland (HIPS);Saarland University, Building A4.1, 66123 Saarbruecken, Germany.
2015-09-09T13:13:55Z
2015-09-09T13:13:55Z
2015-06
Semi-automated nanoprecipitation-system--an option for operator independent, scalable and size adjustable nanoparticle synthesis. 2015, 32 (6):1859-63 Pharm. Res.
1573-904X
25547536
10.1007/s11095-014-1612-z
http://hdl.handle.net/10033/577016
Pharmaceutical research
The preparation of nano-sized carrier systems increasingly moved into focus of pharmaceutical research and industry in the past decades. Besides the drug load and properties of the selected polymer/lipid, the size of such particles is one of the most important parameters regarding their use as efficient drug delivery systems. However, the preparation of nanoparticles with different sizes in a controlled manner is challenging, especially in terms of reproducibility and scale-up possibility. To overcome these hurdles we developed a system relying on nanoprecipitation, which meets all these requirements of an operator independent, scalable and size-adjustable nanoparticle synthesis-the Semi-Automated Nanoprecipitation-System. This system enables the adaption of the particle size to specific needs based on the process parameters-injection rate, flow rate and polymer concentration-identified within this study. The basic set-up is composed of a syringe pump and a gear pump for a precise control of the flow and injection speed of the system. Furthermore, a home-made tube-straightener guarantees a curvature-free injection point. Thus it could be shown that the production of poly(lactide-co-glycolide) nanoparticles from 150 to 600 nm with a narrow size distribution in a controlled semi-automatic manner is possible.
en
Semi-automated nanoprecipitation-system--an option for operator independent, scalable and size adjustable nanoparticle synthesis.
Article
2016-06-01T00:00:00Z
The preparation of nano-sized carrier systems increasingly moved into focus of pharmaceutical research and industry in the past decades. Besides the drug load and properties of the selected polymer/lipid, the size of such particles is one of the most important parameters regarding their use as efficient drug delivery systems. However, the preparation of nanoparticles with different sizes in a controlled manner is challenging, especially in terms of reproducibility and scale-up possibility. To overcome these hurdles we developed a system relying on nanoprecipitation, which meets all these requirements of an operator independent, scalable and size-adjustable nanoparticle synthesis-the Semi-Automated Nanoprecipitation-System. This system enables the adaption of the particle size to specific needs based on the process parameters-injection rate, flow rate and polymer concentration-identified within this study. The basic set-up is composed of a syringe pump and a gear pump for a precise control of the flow and injection speed of the system. Furthermore, a home-made tube-straightener guarantees a curvature-free injection point. Thus it could be shown that the production of poly(lactide-co-glycolide) nanoparticles from 150 to 600 nm with a narrow size distribution in a controlled semi-automatic manner is possible.
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MD5
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TEXT
Rietscher et al_final.pdf.txt
Rietscher et al_final.pdf.txt
Extracted Text
text/plain
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https://hzi.openrepository.com/bitstream/10033/577016/8/Rietscher%20et%20al_final.pdf.txt
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MD5
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THUMBNAIL
Rietscher et al_final.pdf.jpg
Rietscher et al_final.pdf.jpg
Generated Thumbnail
image/jpeg
29916
https://hzi.openrepository.com/bitstream/10033/577016/9/Rietscher%20et%20al_final.pdf.jpg
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MD5
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10033/577016
oai:hzi.openrepository.com:10033/577016
2019-08-30 11:36:32.815
Helmholtz Zentrum für Infektionsforschung Repository
hzi@openrepository.com
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oai:repository.helmholtz-hzi.de:10033/5786732019-08-30T11:36:32Zcom_10033_620613col_10033_620614
Schiller, Stefan
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Hanefeld, Andrea
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Schneider, Marc
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Lehr, Claus-Michael
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Helmholtz Institute for Pharmaceutical Research Saarland,Saarbru¨ cken, Saarland 66123, Germany.
2015-09-24T08:32:31Z
2015-09-24T08:32:31Z
2015-09
Focused Ultrasound as a Scalable and Contact-Free Method to Manufacture Protein-Loaded PLGA Nanoparticles. 2015, 32 (9):2995-3006 Pharm. Res.
1573-904X
25823648
10.1007/s11095-015-1681-7
http://hdl.handle.net/10033/578673
Pharmaceutical research
Although nanomaterials are under investigation for a very broad range of medical applications, only a small fraction of these are already commercialized or in clinical development. A major challenge for the translation of nanomedicines into the clinic is the missing scalability of the available lab scale preparation methods and, ultimately, non-identical samples during early and late research.
en
Focused Ultrasound as a Scalable and Contact-Free Method to Manufacture Protein-Loaded PLGA Nanoparticles.
Article
2016-09-15T00:00:00Z
Although nanomaterials are under investigation for a very broad range of medical applications, only a small fraction of these are already commercialized or in clinical development. A major challenge for the translation of nanomedicines into the clinic is the missing scalability of the available lab scale preparation methods and, ultimately, non-identical samples during early and late research.
ORIGINAL
Schiller Focused Ultrasound - Electronic Supplementary Material.pdf
Schiller Focused Ultrasound - Electronic Supplementary Material.pdf
supplemental materials
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MD5
2
true
Schiller et al_final.pdf
Schiller et al_final.pdf
original manuscript with figures
application/pdf
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https://hzi.openrepository.com/bitstream/10033/578673/1/Schiller%20et%20al_final.pdf
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MD5
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CC-LICENSE
license_url
license_url
text/plain
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https://hzi.openrepository.com/bitstream/10033/578673/3/license_url
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MD5
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license_text
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application/octet-stream
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MD5
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license_rdf
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MD5
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LICENSE
license.txt
license.txt
text/plain
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MD5
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false
TEXT
Schiller Focused Ultrasound - Electronic Supplementary Material.pdf.txt
Schiller Focused Ultrasound - Electronic Supplementary Material.pdf.txt
Extracted Text
text/plain
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https://hzi.openrepository.com/bitstream/10033/578673/11/Schiller%20Focused%20Ultrasound%20-%20Electronic%20Supplementary%20Material.pdf.txt
7489378d1326f0242d2ff215040e2a17
MD5
11
false
Schiller et al_final.pdf.txt
Schiller et al_final.pdf.txt
Extracted Text
text/plain
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https://hzi.openrepository.com/bitstream/10033/578673/12/Schiller%20et%20al_final.pdf.txt
d70caa0176239ec93ddfcd96fcc8ea8c
MD5
12
false
THUMBNAIL
Schiller Focused Ultrasound - Electronic Supplementary Material.pdf.jpg
Schiller Focused Ultrasound - Electronic Supplementary Material.pdf.jpg
Generated Thumbnail
image/jpeg
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https://hzi.openrepository.com/bitstream/10033/578673/15/Schiller%20Focused%20Ultrasound%20-%20Electronic%20Supplementary%20Material.pdf.jpg
db504232edf2c6e53cdb31f1d6493e07
MD5
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false
Schiller et al_final.pdf.jpg
Schiller et al_final.pdf.jpg
Generated Thumbnail
image/jpeg
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MD5
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false
10033/578673
oai:hzi.openrepository.com:10033/578673
2019-08-30 11:36:32.926
Helmholtz Zentrum für Infektionsforschung Repository
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oai:repository.helmholtz-hzi.de:10033/5817982019-08-30T11:32:13Zcom_10033_620613col_10033_620614
Gordon, Sarah
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Helmholtz Institute for Pharmaceutical Research Saarland (HIPS), Campus C23, D-66123 Saarbrücken, Germany.
2015-11-05T09:43:46Z
2015-11-05T09:43:46Z
2015
Non-animal models of epithelial barriers (skin, intestine and lung) in research, industrial applications and regulatory toxicology 2015, 32 (4):327 ALTEX
1868596X
10.14573/altex.1510051
http://hdl.handle.net/10033/581798
ALTEX
http://www.altex.ch/All-issues/Issue.50.html?iid=155&aid=8
Non-animal models of epithelial barriers (skin, intestine and lung) in research, industrial applications and regulatory toxicology
Meetings and Proceedings
2018-06-13T07:36:09Z
ORIGINAL
Gordon et al_final.pdf
Gordon et al_final.pdf
Open Access publication
application/pdf
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https://hzi.openrepository.com/bitstream/10033/581798/1/Gordon%20et%20al_final.pdf
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MD5
1
true
CC-LICENSE
license_url
license_url
text/plain
49
https://hzi.openrepository.com/bitstream/10033/581798/2/license_url
924993ce0b3ba389f79f32a1b2735415
MD5
2
false
license_text
license_text
application/octet-stream
21597
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54dd59d40230fe99c6f8f5992623f9e2
MD5
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license_rdf
license_rdf
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23748
https://hzi.openrepository.com/bitstream/10033/581798/4/license_rdf
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MD5
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LICENSE
license.txt
license.txt
text/plain
1685
https://hzi.openrepository.com/bitstream/10033/581798/5/license.txt
cb598eeb10bfed09d26fd8d285172ad4
MD5
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TEXT
Gordon et al_final.pdf.txt
Gordon et al_final.pdf.txt
Extracted Text
text/plain
310948
https://hzi.openrepository.com/bitstream/10033/581798/6/Gordon%20et%20al_final.pdf.txt
1d3092bccb50a0930b113f0f186b12fc
MD5
6
false
THUMBNAIL
Gordon et al_final.pdf.jpg
Gordon et al_final.pdf.jpg
Generated Thumbnail
image/jpeg
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https://hzi.openrepository.com/bitstream/10033/581798/7/Gordon%20et%20al_final.pdf.jpg
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MD5
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10033/581798
oai:hzi.openrepository.com:10033/581798
2019-08-30 11:32:13.802
Helmholtz Zentrum für Infektionsforschung Repository
hzi@openrepository.com
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Salomon, Johanna J
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Schneider-Daum, Nicole
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Lehr, Claus-Michael
e25b30ba80302580419199334c0f4c6b
500
Ehrhardt, Carsten
80cf54aec838055398a09e09b1f9cd0b
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Helmholtz Institute for Pharmaceutical Research Saarland (HIPS);Saarland University, Building A4.1, 66123 Saarbruecken, Germany.
2015-11-27T14:45:46Z
2015-11-27T14:45:46Z
2015-12-01
Organic cation transporter function in different in vitro models of human lung epithelium. 2015, 80:82-8 Eur J Pharm Sci
1879-0720
26296865
10.1016/j.ejps.2015.08.007
http://hdl.handle.net/10033/582803
European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences
Organic cation transporters (OCT) encoded by members of the solute carrier (SLC) 22 family of genes are involved in the disposition of physiological substrates and xenobiotics, including drugs used in the treatment of chronic obstructive lung diseases and asthma. The aim of this work was to identify continuously growing epithelial cell lines that closely mimic the organic cation transport of freshly isolated human alveolar type I-like epithelial cells (ATI) in primary culture, and which consequently, can be utilised as in vitro models for the study of organic cation transport at the air-blood barrier. OCT activity was investigated by measuring [(14)C]-tetraethylammonium (TEA) uptake into monolayers of Calu-3, NCI-H441 and A549 lung epithelial cell lines in comparison to ATI-like cell monolayers in primary culture. Levels of time-dependent TEA uptake were highest in A549 and ATI-like cells. In A549 cells, TEA uptake had a saturable and a non-saturable component with Km=528.5±373.1μM, Vmax=0.3±0.1nmol/min/mg protein and Kd=0.02μl/min/mg protein. TEA uptake into Calu-3 and NCI-H441 cells did not reach saturation within the concentration range studied. RNAi experiments in A549 cells confirmed that TEA uptake was mainly facilitated by OCT1 and OCT2. Co-incubation studies using pharmacological OCT modulators suggested that organic cation uptake pathways share several similarities between ATI-like primary cells and the NCI-H441 cell line, whereas more pronounced differences exist between primary cells and the A549 and Calu-3 cell lines.
en
Organic cation transporter function in different in vitro models of human lung epithelium.
Article
2016-09-01T00:00:00Z
Organic cation transporters (OCT) encoded by members of the solute carrier (SLC) 22 family of genes are involved in the disposition of physiological substrates and xenobiotics, including drugs used in the treatment of chronic obstructive lung diseases and asthma. The aim of this work was to identify continuously growing epithelial cell lines that closely mimic the organic cation transport of freshly isolated human alveolar type I-like epithelial cells (ATI) in primary culture, and which consequently, can be utilised as in vitro models for the study of organic cation transport at the air-blood barrier. OCT activity was investigated by measuring [(14)C]-tetraethylammonium (TEA) uptake into monolayers of Calu-3, NCI-H441 and A549 lung epithelial cell lines in comparison to ATI-like cell monolayers in primary culture. Levels of time-dependent TEA uptake were highest in A549 and ATI-like cells. In A549 cells, TEA uptake had a saturable and a non-saturable component with Km=528.5±373.1μM, Vmax=0.3±0.1nmol/min/mg protein and Kd=0.02μl/min/mg protein. TEA uptake into Calu-3 and NCI-H441 cells did not reach saturation within the concentration range studied. RNAi experiments in A549 cells confirmed that TEA uptake was mainly facilitated by OCT1 and OCT2. Co-incubation studies using pharmacological OCT modulators suggested that organic cation uptake pathways share several similarities between ATI-like primary cells and the NCI-H441 cell line, whereas more pronounced differences exist between primary cells and the A549 and Calu-3 cell lines.
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oai:repository.helmholtz-hzi.de:10033/5828062019-08-30T11:34:21Zcom_10033_620613col_10033_620614
Schneider, Marc
43297aa0fabdc7552ad4154ab037617a
500
Loretz, Brigitta
caab396a6e6faae9ada274b1a6c40fd5
500
Windbergs, Maike
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Schneider-Daum, Nicole
98160be03011dc8dd14cdc48fbd09cb5
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Schaefer, Ulrich F
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500
Lehr, Claus-Michael
e25b30ba80302580419199334c0f4c6b
500
Helmholtz Institute for Pharmaceutical Research Saarland (HIPS);Saarland University, Building A4.1, 66123 Saarbruecken, Germany.
2015-11-27T15:17:32Z
2015-11-27T15:17:32Z
2015-09
Biological barriers - Advanced drug delivery, in vitro modelling, and their implications for infection research. 2015, 95 (Pt A):1-2 Eur J Pharm Biopharm
1873-3441
26259783
10.1016/j.ejpb.2015.08.003
http://hdl.handle.net/10033/582806
European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft für Pharmazeutische Verfahrenstechnik e.V
en
Biological barriers - Advanced drug delivery, in vitro modelling, and their implications for infection research.
Article
2016-09-01T00:00:00Z
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hzi@openrepository.com
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oai:repository.helmholtz-hzi.de:10033/5835112019-08-30T11:34:22Zcom_10033_620613col_10033_620614
Tscheka, Clemens
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500
Hittinger, Marius
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500
Lehr, Claus-Michael
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Schneider-Daum, Nicole
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Schneider, Marc
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Helmholtz Institute for Pharmaceutical Research Saarland (HIPS);Saarland University, Building A4.1, 66123 Saarbruecken, Germany.
2015-12-09T15:18:15Z
2015-12-09T15:18:15Z
2015-09
Macrophage uptake of cylindrical microparticles investigated with correlative microscopy. 2015, 95 (Pt A):151-5 Eur J Pharm Biopharm
1873-3441
25779350
10.1016/j.ejpb.2015.03.010
http://hdl.handle.net/10033/583511
European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft für Pharmazeutische Verfahrenstechnik e.V
Cylindrical particles offer the opportunity to develop controlled and sustained release systems for the respiratory tract. One reason is that macrophages can phagocyte such particles only from either of the two ends. We investigated the uptake behaviour of murine alveolar macrophages incubated with elongated submicron-structured particles. For that purpose, fluorescent model silica nanoparticles were interconnected with the biocompatible polysaccharide agarose, building up cylindrical particles within the pores of track-etched membranes. In contrast to common approaches we determined the uptake at different time points with scanning electron microscopy, fluorescence microscopy, and the combination of both techniques - correlative microscopy (CLEM). As a consequence, we could securely identify uptake events and observe in detail the engulfment of particles and confirm, that phagocytosis could only be observed from the tips of the cylinders. CLEM allowed a comparison of the uptake measured with different techniques at identical macrophages. Qualitative and quantitative evaluation of this cylindrical particle uptake showed substantial differences between fluorescence microscopy, electron microscopy and the combination of both (CLEM) within 24h.
en
Macrophage uptake of cylindrical microparticles investigated with correlative microscopy.
Article
2016-09-15T00:00:00Z
Cylindrical particles offer the opportunity to develop controlled and sustained release systems for the respiratory tract. One reason is that macrophages can phagocyte such particles only from either of the two ends. We investigated the uptake behaviour of murine alveolar macrophages incubated with elongated submicron-structured particles. For that purpose, fluorescent model silica nanoparticles were interconnected with the biocompatible polysaccharide agarose, building up cylindrical particles within the pores of track-etched membranes. In contrast to common approaches we determined the uptake at different time points with scanning electron microscopy, fluorescence microscopy, and the combination of both techniques - correlative microscopy (CLEM). As a consequence, we could securely identify uptake events and observe in detail the engulfment of particles and confirm, that phagocytosis could only be observed from the tips of the cylinders. CLEM allowed a comparison of the uptake measured with different techniques at identical macrophages. Qualitative and quantitative evaluation of this cylindrical particle uptake showed substantial differences between fluorescence microscopy, electron microscopy and the combination of both (CLEM) within 24h.
ORIGINAL
Tscheka et al.pdf
Tscheka et al.pdf
original manuscript
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oai:hzi.openrepository.com:10033/583511
2019-08-30 11:34:22.477
Helmholtz Zentrum für Infektionsforschung Repository
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oai:repository.helmholtz-hzi.de:10033/5928202019-08-30T11:32:17Zcom_10033_620613col_10033_620614
Schwagerus, Elena
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Sladek, Svenja
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Buckley, Stephen T
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Armas-Capote, Natalia
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Alvarez de la Rosa, Diego
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Harvey, Brian J
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Fischer, Horst
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Illek, Beate
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Huwer, Hanno
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Schneider-Daum, Nicole
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Helmholtz Institute for Pharmaceutical Research Saarland, 66123 Saarbrücken, Germany
2016-01-05T09:05:20Z
2016-01-05T09:05:20Z
2015-11
Expression and function of the epithelial sodium channel δ-subunit in human respiratory epithelial cells in vitro. 2015, 467 (11):2257-73 Pflugers Arch.
1432-2013
25677639
10.1007/s00424-015-1693-5
http://hdl.handle.net/10033/592820
Pflügers Archiv : European journal of physiology
Using human airway epithelial cell lines (i.e. NCI-H441 and Calu-3) as well as human alveolar epithelial type I-like (ATI) cells in primary culture, we studied the contribution of the epithelial sodium channel δ-subunit (δ-ENaC) to transepithelial sodium transport in human lung in vitro. Endogenous δ-ENaC protein was present in all three cell types tested; however, protein abundance was low, and no expression was detected in the apical cell membrane of these cells. Similarly, known modulators of δ-ENaC activity, such as capsazepine and icilin (activators) and Evans blue (inhibitor), did not show effects on short-circuit current (I SC), suggesting that δ-ENaC is not involved in the modulation of transcellular sodium absorption in NCI-H441 cell monolayers. Over-expression of δ-ENaC in NCI-H441 cells resulted in detectable protein expression in the apical cell membrane, as well as capsazepine and icilin-stimulated increases in I SC that were effectively blocked by Evans blue and that were consistent with δ-ENaC activation and inhibition, respectively. Consequently, these observations suggest that δ-ENaC expression is low in NCI-H441, Calu-3, and ATI cells and does not contribute to transepithelial sodium absorption.
en
Expression and function of the epithelial sodium channel δ-subunit in human respiratory epithelial cells in vitro.
Article
2016-11-15T00:00:00Z
Using human airway epithelial cell lines (i.e. NCI-H441 and Calu-3) as well as human alveolar epithelial type I-like (ATI) cells in primary culture, we studied the contribution of the epithelial sodium channel δ-subunit (δ-ENaC) to transepithelial sodium transport in human lung in vitro. Endogenous δ-ENaC protein was present in all three cell types tested; however, protein abundance was low, and no expression was detected in the apical cell membrane of these cells. Similarly, known modulators of δ-ENaC activity, such as capsazepine and icilin (activators) and Evans blue (inhibitor), did not show effects on short-circuit current (I SC), suggesting that δ-ENaC is not involved in the modulation of transcellular sodium absorption in NCI-H441 cell monolayers. Over-expression of δ-ENaC in NCI-H441 cells resulted in detectable protein expression in the apical cell membrane, as well as capsazepine and icilin-stimulated increases in I SC that were effectively blocked by Evans blue and that were consistent with δ-ENaC activation and inhibition, respectively. Consequently, these observations suggest that δ-ENaC expression is low in NCI-H441, Calu-3, and ATI cells and does not contribute to transepithelial sodium absorption.
ORIGINAL
Schwagerus et al.pdf
Schwagerus et al.pdf
original manuscript
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Schwagerus et al.pdf.txt
Schwagerus et al.pdf.txt
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MD5
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THUMBNAIL
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2019-08-30 11:32:17.171
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oai:repository.helmholtz-hzi.de:10033/5936882019-08-30T11:28:51Zcom_10033_620613col_10033_620614
Dimer, Frantiescoli
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500
de Souza Carvalho-Wodarz, Cristiane
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Haupenthal, Jörg
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Hartmann, Rolf
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Lehr, Claus-Michael
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Helmholtz-Institute for Pharmaceutical 8 Research Saarland (HIPS),Saarland 9 University, 66123 Saarbrücken, Germany.
2016-01-18T10:41:31Z
2016-01-18T10:41:31Z
2015-12
Inhalable Clarithromycin Microparticles for Treatment of Respiratory Infections. 2015, 32 (12):3850-61 Pharm. Res.
1573-904X
26113237
10.1007/s11095-015-1745-8
http://hdl.handle.net/10033/593688
Pharmaceutical research
The aim of this work was to develop clarithromycin microparticles (CLARI-MP) and evaluate their aerodynamic behavior, safety in bronchial cells and anti-bacterial efficacy.
en
Inhalable Clarithromycin Microparticles for Treatment of Respiratory Infections.
Article
2016-12-15T00:00:00Z
The aim of this work was to develop clarithromycin microparticles (CLARI-MP) and evaluate their aerodynamic behavior, safety in bronchial cells and anti-bacterial efficacy.
ORIGINAL
PHAM-S-15-00176-1_cut.pdf
PHAM-S-15-00176-1_cut.pdf
submitted manuscript
application/pdf
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https://hzi.openrepository.com/bitstream/10033/593688/1/PHAM-S-15-00176-1_cut.pdf
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MD5
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true
CC-LICENSE
license_url
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text/plain
49
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MD5
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license_text
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LICENSE
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text/plain
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MD5
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TEXT
PHAM-S-15-00176-1_cut.pdf.txt
PHAM-S-15-00176-1_cut.pdf.txt
Extracted Text
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THUMBNAIL
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Generated Thumbnail
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10033/593688
oai:hzi.openrepository.com:10033/593688
2019-08-30 11:28:51.565
Helmholtz Zentrum für Infektionsforschung Repository
hzi@openrepository.com
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oai:repository.helmholtz-hzi.de:10033/5958782019-08-30T11:34:17Zcom_10033_620613col_10033_620614
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Helmholtz Institute for Pharmaceutical Research Saarland (HIPS);Saarland University, Building A4.1, 66123 Saarbruecken, Germany.
2016-02-08T13:00:22Z
2016-02-08T13:00:22Z
2016-02
Dual flow bioreactor with ultrathin microporous TEER sensing membrane for evaluation of nanoparticle toxicity 2016, 223:440 Sensors and Actuators B: Chemical
09254005
10.1016/j.snb.2015.09.078
http://hdl.handle.net/10033/595878
Sensors and Actuators B: Chemical
http://linkinghub.elsevier.com/retrieve/pii/S0925400515303853
Dual flow bioreactor with ultrathin microporous TEER sensing membrane for evaluation of nanoparticle toxicity
Article
2017-02-15T00:00:00Z
ORIGINAL
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Sbrana et al.pdf
accepted manuscript
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2019-08-30 11:34:17.591
Helmholtz Zentrum für Infektionsforschung Repository
hzi@openrepository.com
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oai:repository.helmholtz-hzi.de:10033/5959592019-08-30T11:33:57Zcom_10033_620613col_10033_620614
Labouta, Hagar Ibrahim
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Menina, Sara
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Kochut, Annika
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Gordon, Sarah
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Geyer, Rebecca
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Dersch, Petra
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Lehr, Claus-Michael
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Helmholtz Institute for Pharmaceutical Research Saarland (HIPS);Saarland University, Building A4.1, 66123 Saarbruecken, Germany.
2016-02-09T13:56:58Z
2016-02-09T13:56:58Z
2015-12-28
Bacteriomimetic invasin-functionalized nanocarriers for intracellular delivery. 2015, 220 (Pt A):414-24 J Control Release
1873-4995
26522071
10.1016/j.jconrel.2015.10.052
http://hdl.handle.net/10033/595959
Journal of controlled release : official journal of the Controlled Release Society
Intracellular bacteria invade mammalian cells to establish an infectious niche. The current work models adhesion and subsequent internalization strategy of pathogenic bacteria into mammalian cells to design a bacteriomimetic bioinvasive delivery system. We report on the surface functionalization of liposomes with a C-terminal fragment of invasin (InvA497), an invasion factor in the outer membrane of Yersinia pseudotuberculosis. InvA497-functionalized liposomes adhere to mammalian epithelial HEp-2 cell line at different infection stages with a significantly higher efficiency than liposomes functionalized with bovine serum albumin. Covalent attachment of InvA497 results in higher cellular adhesion than liposomes with physically adsorbed InvA497 with non-specific surface protein alignment. Uptake studies in HEp-2 cells indicate active internalization of InvA497-functionalized liposomes via β1-integrin receptor-mediated uptake mechanism mimicking the natural invasion strategy of Y. pseudotuberculosis. Uptake studies in Caco-2 cells at different polarization states demonstrate specific targeting of the InvA497-functionalized liposomes to less polarized cells reflecting the status of inflamed cells. Moreover, when loaded with the anti-infective agent gentamicin and applied to HEp-2 cells infected with Y. pseudotuberculosis, InvA497-functionalized liposomes are able to significantly reduce the infection load relative to non-functionalized drug-loaded liposomes. This indicates a promising application of such a bacteriomimetic system for drug delivery to intracellular compartments.
en
Bacteriomimetic invasin-functionalized nanocarriers for intracellular delivery.
Article
2016-12-15T00:00:00Z
Intracellular bacteria invade mammalian cells to establish an infectious niche. The current work models adhesion and subsequent internalization strategy of pathogenic bacteria into mammalian cells to design a bacteriomimetic bioinvasive delivery system. We report on the surface functionalization of liposomes with a C-terminal fragment of invasin (InvA497), an invasion factor in the outer membrane of Yersinia pseudotuberculosis. InvA497-functionalized liposomes adhere to mammalian epithelial HEp-2 cell line at different infection stages with a significantly higher efficiency than liposomes functionalized with bovine serum albumin. Covalent attachment of InvA497 results in higher cellular adhesion than liposomes with physically adsorbed InvA497 with non-specific surface protein alignment. Uptake studies in HEp-2 cells indicate active internalization of InvA497-functionalized liposomes via β1-integrin receptor-mediated uptake mechanism mimicking the natural invasion strategy of Y. pseudotuberculosis. Uptake studies in Caco-2 cells at different polarization states demonstrate specific targeting of the InvA497-functionalized liposomes to less polarized cells reflecting the status of inflamed cells. Moreover, when loaded with the anti-infective agent gentamicin and applied to HEp-2 cells infected with Y. pseudotuberculosis, InvA497-functionalized liposomes are able to significantly reduce the infection load relative to non-functionalized drug-loaded liposomes. This indicates a promising application of such a bacteriomimetic system for drug delivery to intracellular compartments.
ORIGINAL
Labouta, J. Control. Rel., 2015.pdf
Labouta, J. Control. Rel., 2015.pdf
accepted manuscript
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Labouta, J. Control. Rel., 2015.pdf.txt
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THUMBNAIL
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2019-08-30 11:33:57.428
Helmholtz Zentrum für Infektionsforschung Repository
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oai:repository.helmholtz-hzi.de:10033/5959662019-08-30T11:30:58Zcom_10033_620613col_10033_620614
Guillot, Alexis
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Helmholtz Institute for Pharmaceutical Research Saarland (HIPS);Saarland University, Building A4.1, 66123 Saarbruecken, Germany.
2016-02-09T15:11:50Z
2016-02-09T15:11:50Z
2015-12
Solid Phase Extraction as an Innovative Separation Method for Measuring Free and Entrapped Drug in Lipid Nanoparticles. 2015, 32 (12):3999-4009 Pharm. Res.
1573-904X
26202518
10.1007/s11095-015-1761-8
http://hdl.handle.net/10033/595966
Pharmaceutical research
Contrary to physical characterization techniques for nanopharmaceuticals (shape, size and zeta-potential), the techniques to quantify the free and the entrapped drug remain very few and difficult to transpose in routine analytical laboratories. The application of Solid Phase Extraction (SPE) technique was investigated to overcome this challenge.
en
Solid Phase Extraction as an Innovative Separation Method for Measuring Free and Entrapped Drug in Lipid Nanoparticles.
Article
2016-08-01T00:00:00Z
Contrary to physical characterization techniques for nanopharmaceuticals (shape, size and zeta-potential), the techniques to quantify the free and the entrapped drug remain very few and difficult to transpose in routine analytical laboratories. The application of Solid Phase Extraction (SPE) technique was investigated to overcome this challenge.
ORIGINAL
Guilot et al.pdf
Guilot et al.pdf
original manuscript with figures
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Helmholtz Zentrum für Infektionsforschung Repository
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oai:repository.helmholtz-hzi.de:10033/5967202019-08-30T11:33:57Zcom_10033_620613col_10033_620614
Selzer, Dominik
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500
Neumann, Dirk
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Neumann, Heike
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Kostka, Karl-Heinz
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Lehr, Claus-Michael
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Schaefer, Ulrich F
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Helmholtz Institute for Pharmaceutical Research Saarland (HIPS);Saarland University, Building A4.1, 66123 Saarbruecken, Germany.
2016-02-19T14:20:28Z
2016-02-19T14:20:28Z
2015-09
A strategy for in-silico prediction of skin absorption in man. 2015, 95 (Pt A):68-76 Eur J Pharm Biopharm
1873-3441
26022643
10.1016/j.ejpb.2015.05.002
http://hdl.handle.net/10033/596720
European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft für Pharmazeutische Verfahrenstechnik e.V
For some time, in-silico models to address substance transport into and through the skin are gaining more and more importance in different fields of science and industry. In particular, the mathematical prediction of in-vivo skin absorption is of great interest to overcome ethical and economical issues. The presented work outlines a strategy to address this problem and in particular, investigates in-vitro and in-vivo skin penetration experiments of the model compound flufenamic acid solved in an ointment by means of a mathematical model. Experimental stratum corneum concentration-depth profiles (SC-CDP) for various time intervals using two different in-vitro systems (Franz diffusion cell, Saarbruecken penetration model) were examined and simulated with the help of a highly optimized three compartment numerical diffusion model and compared to the findings of SC-CDPs of the in-vivo scenario. Fitted model input parameters (diffusion coefficient and partition coefficient with respect to the stratum corneum) for the in-vitro infinite dose case could be used to predict the in-use conditions in-vitro. Despite apparent differences in calculated partition coefficients between in-vivo and in-vitro studies, prediction of in-vivo scenarios from input parameters calculated from the in-vitro case yielded reasonable results.
en
A strategy for in-silico prediction of skin absorption in man.
Article
2016-09-01T00:00:00Z
For some time, in-silico models to address substance transport into and through the skin are gaining more and more importance in different fields of science and industry. In particular, the mathematical prediction of in-vivo skin absorption is of great interest to overcome ethical and economical issues. The presented work outlines a strategy to address this problem and in particular, investigates in-vitro and in-vivo skin penetration experiments of the model compound flufenamic acid solved in an ointment by means of a mathematical model. Experimental stratum corneum concentration-depth profiles (SC-CDP) for various time intervals using two different in-vitro systems (Franz diffusion cell, Saarbruecken penetration model) were examined and simulated with the help of a highly optimized three compartment numerical diffusion model and compared to the findings of SC-CDPs of the in-vivo scenario. Fitted model input parameters (diffusion coefficient and partition coefficient with respect to the stratum corneum) for the in-vitro infinite dose case could be used to predict the in-use conditions in-vitro. Despite apparent differences in calculated partition coefficients between in-vivo and in-vitro studies, prediction of in-vivo scenarios from input parameters calculated from the in-vitro case yielded reasonable results.
ORIGINAL
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oai:repository.helmholtz-hzi.de:10033/5969672019-08-30T11:34:22Zcom_10033_620613col_10033_620614
Kenngott, Elisabeth E
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Schmitt, Manfred J
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Breinig, Frank
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Helmholtz Institute for Pharmaceutical Research Saarland (HIPS);Saarland University, Building A4.1, 66123 Saarbruecken, Germany.
2016-02-23T14:20:57Z
2016-02-23T14:20:57Z
2016-02-28
Surface-modified yeast cells: A novel eukaryotic carrier for oral application. 2016, 224:1-7 J Control Release
1873-4995
26763373
10.1016/j.jconrel.2015.12.054
http://hdl.handle.net/10033/596967
Journal of controlled release : official journal of the Controlled Release Society
The effective targeting and subsequent binding of particulate carriers to M cells in Peyer's patches of the gut is a prerequisite for the development of oral delivery systems. We have established a novel carrier system based on cell surface expression of the β1-integrin binding domain of invasins derived from Yersinia enterocolitica and Yersinia pseudotuberculosis on the yeast Saccharomyces cerevisiae. All invasin derivatives were shown to be effectively expressed on the cell surface and recombinant yeast cells showed improved binding to both human HEp-2 cells and M-like cells in vitro. Among the different derivatives tested, the integrin-binding domain of Y. enterocolitica invasin proved to be the most effective and was able to target Peyer's patches in vivo. In conclusion, cell surface-modified yeasts might provide a novel bioadhesive, eukaryotic carrier system for efficient and targeted delivery of either antigens or drugs via the oral route.
en
Surface-modified yeast cells: A novel eukaryotic carrier for oral application.
Article
2017-03-01T00:00:00Z
The effective targeting and subsequent binding of particulate carriers to M cells in Peyer's patches of the gut is a prerequisite for the development of oral delivery systems. We have established a novel carrier system based on cell surface expression of the β1-integrin binding domain of invasins derived from Yersinia enterocolitica and Yersinia pseudotuberculosis on the yeast Saccharomyces cerevisiae. All invasin derivatives were shown to be effectively expressed on the cell surface and recombinant yeast cells showed improved binding to both human HEp-2 cells and M-like cells in vitro. Among the different derivatives tested, the integrin-binding domain of Y. enterocolitica invasin proved to be the most effective and was able to target Peyer's patches in vivo. In conclusion, cell surface-modified yeasts might provide a novel bioadhesive, eukaryotic carrier system for efficient and targeted delivery of either antigens or drugs via the oral route.
ORIGINAL
Kenngott et al.pdf
Kenngott et al.pdf
original manuscript with figures
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Mathes, C
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Melero, A
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Vogt, T
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De Rossi, C
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Garrigues, T M
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Hansen, S
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Guterres, S S
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Pohlmann, A R
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Beck, R C R
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Lehr, C-M
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Schaefer, U F
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Helmholtz Institute for Pharmaceutical Research Saarland (HIPS);Saarland University, Building A4.1, 66123 Saarbruecken, Germany.
2016-02-26T15:11:24Z
2016-02-26T15:11:24Z
2016-02-10
Nanocarriers for optimizing the balance between interfollicular permeation and follicular uptake of topically applied clobetasol to minimize adverse effects. 2016, 223:207-14 J Control Release
1873-4995
26686081
10.1016/j.jconrel.2015.12.010
http://hdl.handle.net/10033/599290
Journal of controlled release : official journal of the Controlled Release Society
The treatment of various hair disorders has become a central focus of good dermatologic patient care as it affects men and women all over the world. For many inflammatory-based scalp diseases, glucocorticoids are an essential part of treatment, even though they are known to cause systemic as well as local adverse effects when applied topically. Therefore, efficient targeting and avoidance of these side effects are of utmost importance. Optimizing the balance between drug release, interfollicular permeation, and follicular uptake may allow minimizing these adverse events and simultaneously improve drug delivery, given that one succeeds in targeting a sustained release formulation to the hair follicle. To test this hypothesis, three types of polymeric nanocarriers (nanospheres, nanocapsules, lipid-core nanocapsules) for the potent glucocorticoid clobetasol propionate (CP) were prepared. They all exhibited a sustained release of drug, as was desired. The particles were formulated as a dispersion and hydrogel and (partially) labeled with Rhodamin B for quantification purposes. Follicular uptake was investigated using the Differential Stripping method and was found highest for nanocapsules in dispersion after application of massage. Moreover, the active ingredient (CP) as well as the nanocarrier (Rhodamin B labeled polymer) recovered in the hair follicle were measured simultaneously, revealing an equivalent uptake of both. In contrast, only negligible amounts of CP could be detected in the hair follicle when applied as free drug in solution or hydrogel, regardless of any massage. Skin permeation experiments using heat-separated human epidermis mounted in Franz Diffusion cells revealed equivalent reduced transdermal permeability for all nanocarriers in comparison to application of the free drug. Combining these results, nanocapsules formulated as an aqueous dispersion and applied by massage appeare to be a good candidate to maximize follicular targeting and minimize drug penetration into the interfollicular epidermis. We conclude that such nanotechnology-based formulations provide a viable strategy for more efficient drug delivery to the hair follicle. Moreover, they present a way to minimize adverse effects of potent glucocorticoids by releasing the drug in a controlled manner and simultaneously decreasing interfollicular permeation, offering an advantage over conventional formulations for inflammatory-based skin/scalp diseases.
en
Nanocarriers for optimizing the balance between interfollicular permeation and follicular uptake of topically applied clobetasol to minimize adverse effects.
Article
2017-02-15T00:00:00Z
The treatment of various hair disorders has become a central focus of good dermatologic patient care as it affects men and women all over the world. For many inflammatory-based scalp diseases, glucocorticoids are an essential part of treatment, even though they are known to cause systemic as well as local adverse effects when applied topically. Therefore, efficient targeting and avoidance of these side effects are of utmost importance. Optimizing the balance between drug release, interfollicular permeation, and follicular uptake may allow minimizing these adverse events and simultaneously improve drug delivery, given that one succeeds in targeting a sustained release formulation to the hair follicle. To test this hypothesis, three types of polymeric nanocarriers (nanospheres, nanocapsules, lipid-core nanocapsules) for the potent glucocorticoid clobetasol propionate (CP) were prepared. They all exhibited a sustained release of drug, as was desired. The particles were formulated as a dispersion and hydrogel and (partially) labeled with Rhodamin B for quantification purposes. Follicular uptake was investigated using the Differential Stripping method and was found highest for nanocapsules in dispersion after application of massage. Moreover, the active ingredient (CP) as well as the nanocarrier (Rhodamin B labeled polymer) recovered in the hair follicle were measured simultaneously, revealing an equivalent uptake of both. In contrast, only negligible amounts of CP could be detected in the hair follicle when applied as free drug in solution or hydrogel, regardless of any massage. Skin permeation experiments using heat-separated human epidermis mounted in Franz Diffusion cells revealed equivalent reduced transdermal permeability for all nanocarriers in comparison to application of the free drug. Combining these results, nanocapsules formulated as an aqueous dispersion and applied by massage appeare to be a good candidate to maximize follicular targeting and minimize drug penetration into the interfollicular epidermis. We conclude that such nanotechnology-based formulations provide a viable strategy for more efficient drug delivery to the hair follicle. Moreover, they present a way to minimize adverse effects of potent glucocorticoids by releasing the drug in a controlled manner and simultaneously decreasing interfollicular permeation, offering an advantage over conventional formulations for inflammatory-based skin/scalp diseases.
ORIGINAL
2-26_JCR Submission final.pdf
2-26_JCR Submission final.pdf
original manuscript with figures and tables
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oai:repository.helmholtz-hzi.de:10033/6003022019-08-30T11:34:43Zcom_10033_620613col_10033_620614
Dandekar, P.
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Jain, R.
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Keil, M.
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Loretz, B.
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Koch, M.
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Wenz, G.
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Lehr, C.-M.
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Helmholtz-Institute for Pharmaceutical Research Saarland (HIPS),Saarland 9 University, 66123 Saarbrücken, Germany.
2016-02-29T10:30:28Z
2016-02-29T10:30:28Z
2015
Enhanced uptake and siRNA-mediated knockdown of a biologically relevant gene using cyclodextrin polyrotaxane 2015, 3 (13):2590 J. Mater. Chem. B
2050-750X
2050-7518
10.1039/C4TB01821D
http://hdl.handle.net/10033/600302
J. Mater. Chem. B
info:eu-repo/grantAgreement/EC/FP7/229571
http://xlink.rsc.org/?DOI=C4TB01821D
openAccess
Enhanced uptake and siRNA-mediated knockdown of a biologically relevant gene using cyclodextrin polyrotaxane
Article
2018-06-13T07:21:31Z
ORIGINAL
Dandekar et al.pdf
Dandekar et al.pdf
Open Access publication
application/pdf
1099982
https://hzi.openrepository.com/bitstream/10033/600302/1/Dandekar%20et%20al.pdf
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MD5
1
true
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oai:repository.helmholtz-hzi.de:10033/6047462019-08-30T11:26:12Zcom_10033_620613col_10033_620614
Kuehn, Anna
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de Souza Carvalho-Wodarz, Cristiane
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Repnik, Urska
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Griffiths, Gareth
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Fischer, Ulrike
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Meese, Eckart
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Huwer, Hanno
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Wirth, Dagmar
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May, Tobias
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Schneider-Daum, Nicole
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Lehr, Claus Michael
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http://orcid.org/0000-0002-5864-8462
Helmholtz-Institute for Pharmaceutical Research Saarland (HIPS), Saarland University, Campus C2.3, D-66123 Saarbrücken, Germany.
2016-04-07T14:39:20Z
2016-04-07T14:39:20Z
2016-03-17
Human alveolar epithelial cells expressing tight junctions to model the air-blood barrier. 2016: ALTEX
1868-596X
26985677
10.14573/altex.1511131
http://hdl.handle.net/10033/604746
ALTEX
This paper describes a new human alveolar epithelial cell line (hAELVi - human Alveolar Epithelial Lentivirus immortalized) with type I-like characteristics and functional tight junctions, suitable to model the air-blood barrier of the peripheral lung. Primary human alveolar epithelial cells were immortalized by a novel regimen, grown as monolayers on permeable filter supports and characterized morphologically, biochemically and biophysically. hAELVi cells maintain the capacity to form tight intercellular junctions, with high trans-epithelial electrical resistance (> 1000 Ω*cm²). The cells could be kept in culture over several days, up to passage 75, under liquid-liquid as well as air-liquid conditions. Ultrastructural analysis and real time PCR revealed type I-like cell properties, such as the presence of caveolae, expression of caveolin-1, and absence of surfactant protein C. Accounting for the barrier properties, inter-digitations sealed with tight junctions and desmosomes were also observed. Low permeability of the hydrophilic marker sodium fluorescein confirmed the suitability of hAELVi cells for in vitro transport studies across the alveolar epithelium. These results suggest that hAELVi cells reflect the essential features of the air-blood barrier, as needed for an alternative to animal testing to study absorption and toxicity of inhaled drugs, chemicals and nanomaterials.
ENG
Human alveolar epithelial cells expressing tight junctions to model the air-blood barrier.
Article
2018-06-12T22:19:58Z
This paper describes a new human alveolar epithelial cell line (hAELVi - human Alveolar Epithelial Lentivirus immortalized) with type I-like characteristics and functional tight junctions, suitable to model the air-blood barrier of the peripheral lung. Primary human alveolar epithelial cells were immortalized by a novel regimen, grown as monolayers on permeable filter supports and characterized morphologically, biochemically and biophysically. hAELVi cells maintain the capacity to form tight intercellular junctions, with high trans-epithelial electrical resistance (> 1000 Ω*cm²). The cells could be kept in culture over several days, up to passage 75, under liquid-liquid as well as air-liquid conditions. Ultrastructural analysis and real time PCR revealed type I-like cell properties, such as the presence of caveolae, expression of caveolin-1, and absence of surfactant protein C. Accounting for the barrier properties, inter-digitations sealed with tight junctions and desmosomes were also observed. Low permeability of the hydrophilic marker sodium fluorescein confirmed the suitability of hAELVi cells for in vitro transport studies across the alveolar epithelium. These results suggest that hAELVi cells reflect the essential features of the air-blood barrier, as needed for an alternative to animal testing to study absorption and toxicity of inhaled drugs, chemicals and nanomaterials.
ORIGINAL
Kuehn et al.pdf
Kuehn et al.pdf
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THUMBNAIL
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2019-08-30 11:26:12.919
Helmholtz Zentrum für Infektionsforschung Repository
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oai:repository.helmholtz-hzi.de:10033/6091912019-08-30T11:25:11Zcom_10033_620613col_10033_620614
Nguyen, Duc Bach
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Thuy Ly, Thi Bich
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Wesseling, Mauro Carlos
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Hittinger, Marius
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Torge, Afra
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Devitt, Andrew
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Perrie, Yvonne
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Bernhardt, Ingolf
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Helmholtz-Institute for Pharmaceutical Research Saarland (HIPS),Saarland 9 University, 66123 Saarbrücken, Germany.
2016-05-12T14:14:28Z
2016-05-12T14:14:28Z
2016
Characterization of Microvesicles Released from Human Red Blood Cells. 2016, 38 (3):1085-99 Cell. Physiol. Biochem.
1421-9778
26938586
10.1159/000443059
http://hdl.handle.net/10033/609191
Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology
Extracellular vesicles (EVs) are spherical fragments of cell membrane released from various cell types under physiological as well as pathological conditions. Based on their size and origin, EVs are classified as exosome, microvesicles (MVs) and apoptotic bodies. Recently, the release of MVs from human red blood cells (RBCs) under different conditions has been reported. MVs are released by outward budding and fission of the plasma membrane. However, the outward budding process itself, the release of MVs and the physical properties of these MVs have not been well investigated. The aim of this study is to investigate the formation process, isolation and characterization of MVs released from RBCs under conditions of stimulating Ca2+ uptake and activation of protein kinase C.
en
Characterization of Microvesicles Released from Human Red Blood Cells.
Article
2018-06-12T17:43:25Z
Extracellular vesicles (EVs) are spherical fragments of cell membrane released from various cell types under physiological as well as pathological conditions. Based on their size and origin, EVs are classified as exosome, microvesicles (MVs) and apoptotic bodies. Recently, the release of MVs from human red blood cells (RBCs) under different conditions has been reported. MVs are released by outward budding and fission of the plasma membrane. However, the outward budding process itself, the release of MVs and the physical properties of these MVs have not been well investigated. The aim of this study is to investigate the formation process, isolation and characterization of MVs released from RBCs under conditions of stimulating Ca2+ uptake and activation of protein kinase C.
ORIGINAL
Nguyen et al.pdf
Nguyen et al.pdf
Open Access article
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Nguyen et al.pdf.txt
Nguyen et al.pdf.txt
Extracted Text
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THUMBNAIL
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10033/609191
oai:hzi.openrepository.com:10033/609191
2019-08-30 11:25:11.276
Helmholtz Zentrum für Infektionsforschung Repository
hzi@openrepository.com
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oai:repository.helmholtz-hzi.de:10033/6113652019-08-30T11:33:57Zcom_10033_620613col_10033_620614
Rietscher, René
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Czaplewska, Justyna A
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Majdanski, Tobias C
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Gottschaldt, Michael
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Schubert, Ulrich S
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Schneider, Marc
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Lehr, Claus-Michael
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2016-06-01T09:55:59Z
2016-06-01T09:55:59Z
2016-03-16
Impact of PEG and PEG-b-PAGE modified PLGA on nanoparticle formation, protein loading and release. 2016, 500 (1-2):187-95 Int J Pharm
1873-3476
26784983
10.1016/j.ijpharm.2016.01.021
http://hdl.handle.net/10033/611365
International journal of pharmaceutics
The effect of modifying the well-established pharmaceutical polymer PLGA by different PEG-containing block-copolymers on the preparation of ovalbumin (OVA) loaded PLGA nanoparticles (NPs) was studied. The used polymers contained poly(d,l-lactic-co-glycolic acid) (PLGA), polyethylene glycol (PEG) and poly(allyl glycidyl ether) (PAGE) as building blocks. The double emulsion technique yielded spherical NPs in the size range from 170 to 220nm (PDI<0.15) for all the differently modified polymers, allowing to directly compare protein loading of and release. PEGylation is usually believed to increase the hydrophilic character of produced particles, favoring encapsulation of hydrophilic substances. However, in this study simple PEGylation of PLGA had only a slight effect on protein release. In contrast, incorporating a PAGE block between the PEG and PLGA units, also eventually enabling active targeting introducing a reactive group, led to a significantly higher loading (+25%) and release rate (+100%), compared to PLGA and PEG-b-PLGA NPs.
en
Impact of PEG and PEG-b-PAGE modified PLGA on nanoparticle formation, protein loading and release.
Article
2017-03-15T00:00:00Z
The effect of modifying the well-established pharmaceutical polymer PLGA by different PEG-containing block-copolymers on the preparation of ovalbumin (OVA) loaded PLGA nanoparticles (NPs) was studied. The used polymers contained poly(d,l-lactic-co-glycolic acid) (PLGA), polyethylene glycol (PEG) and poly(allyl glycidyl ether) (PAGE) as building blocks. The double emulsion technique yielded spherical NPs in the size range from 170 to 220nm (PDI<0.15) for all the differently modified polymers, allowing to directly compare protein loading of and release. PEGylation is usually believed to increase the hydrophilic character of produced particles, favoring encapsulation of hydrophilic substances. However, in this study simple PEGylation of PLGA had only a slight effect on protein release. In contrast, incorporating a PAGE block between the PEG and PLGA units, also eventually enabling active targeting introducing a reactive group, led to a significantly higher loading (+25%) and release rate (+100%), compared to PLGA and PEG-b-PLGA NPs.
ORIGINAL
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2019-08-30 11:33:57.456
Helmholtz Zentrum für Infektionsforschung Repository
hzi@openrepository.com
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oai:repository.helmholtz-hzi.de:10033/6149162019-08-30T11:34:22Zcom_10033_620613col_10033_620614
Bokkasam, Harish
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Ernst, Matthias
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Guenther, Marco
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Wagner, Christian
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Schaefer, Ulrich F
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Lehr, Claus-Michael
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Helmholtz-Institut für pharmazeutische Forschung Saarland, Universitätscampus E8.1, 66123 Saarbrücken.
2016-06-28T14:04:30Z
2016-06-28T14:04:30Z
2016-06-13
Different macro- and micro-rheological properties of native porcine respiratory and intestinal mucus. 2016: Int J Pharm
1873-3476
27311353
10.1016/j.ijpharm.2016.06.035
http://hdl.handle.net/10033/614916
International journal of pharmaceutics
Aim of this study was to investigate the similarities and differences at macro- and microscale in the viscoelastic properties of mucus that covers the epithelia of the intestinal and respiratory tract. Natural mucus was collected from pulmonary and intestinal regions of healthy pigs. Macro-rheological investigations were carried out through conventional plate-plate rheometry. Microrheology was investigated using optical tweezers. Our data revealed significant differences both in macro- and micro-rheological properties between respiratory and intestinal mucus.
ENG
http://creativecommons.org/licenses/by-nc-sa/4.0/
Different macro- and micro-rheological properties of native porcine respiratory and intestinal mucus.
Article
2017-06-15T00:00:00Z
Aim of this study was to investigate the similarities and differences at macro- and microscale in the viscoelastic properties of mucus that covers the epithelia of the intestinal and respiratory tract. Natural mucus was collected from pulmonary and intestinal regions of healthy pigs. Macro-rheological investigations were carried out through conventional plate-plate rheometry. Microrheology was investigated using optical tweezers. Our data revealed significant differences both in macro- and micro-rheological properties between respiratory and intestinal mucus.
ORIGINAL
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Bokkasam et al.pdf
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Helmholtz Zentrum für Infektionsforschung Repository
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Helmholtz-Institut für Pharmazeutische Forschung Saarland, Universitätscampus E8.1,56123 Saarbrücken, Germany.
2016-07-21T13:21:30Z
2016-07-21T13:21:30Z
2015
Non-animal models of epithelial barriers (skin, intestine and lung) in research, industrial applications and regulatory toxicology. 2015, 32 (4):327-78 ALTEX
1868-596X
26536291
http://hdl.handle.net/10033/617325
ALTEX
Models of the outer epithelia of the human body - namely the skin, the intestine and the lung - have found valid applications in both research and industrial settings as attractive alternatives to animal testing. A variety of approaches to model these barriers are currently employed in such fields, ranging from the utilization of ex vivo tissue to reconstructed in vitro models, and further to chip-based technologies, synthetic membrane systems and, of increasing current interest, in silico modeling approaches. An international group of experts in the field of epithelial barriers was convened from academia, industry and regulatory bodies to present both the current state of the art of non-animal models of the skin, intestinal and pulmonary barriers in their various fields of application, and to discuss research-based, industry-driven and regulatory-relevant future directions for both the development of new models and the refinement of existing test methods. Issues of model relevance and preference, validation and standardization, acceptance, and the need for simplicity versus complexity were focal themes of the discussions. The outcomes of workshop presentations and discussions, in relation to both current status and future directions in the utilization and development of epithelial barrier models, are presented by the attending experts in the current report.
en
http://creativecommons.org/licenses/by-nc-sa/4.0/
Animal Testing Alternatives
Animals
Biomedical Research
Cell Culture Techniques
Epithelial Cells
Humans
Intestines
Lung
Models, Animal
Permeability
Skin
Toxicity Tests
Non-animal models of epithelial barriers (skin, intestine and lung) in research, industrial applications and regulatory toxicology.
Article
2018-06-12T17:18:58Z
Models of the outer epithelia of the human body - namely the skin, the intestine and the lung - have found valid applications in both research and industrial settings as attractive alternatives to animal testing. A variety of approaches to model these barriers are currently employed in such fields, ranging from the utilization of ex vivo tissue to reconstructed in vitro models, and further to chip-based technologies, synthetic membrane systems and, of increasing current interest, in silico modeling approaches. An international group of experts in the field of epithelial barriers was convened from academia, industry and regulatory bodies to present both the current state of the art of non-animal models of the skin, intestinal and pulmonary barriers in their various fields of application, and to discuss research-based, industry-driven and regulatory-relevant future directions for both the development of new models and the refinement of existing test methods. Issues of model relevance and preference, validation and standardization, acceptance, and the need for simplicity versus complexity were focal themes of the discussions. The outcomes of workshop presentations and discussions, in relation to both current status and future directions in the utilization and development of epithelial barrier models, are presented by the attending experts in the current report.
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Helmholtz Zentrum für Infektionsforschung Repository
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oai:repository.helmholtz-hzi.de:10033/6176122019-08-30T11:34:43Zcom_10033_620613col_10033_620614
Buchy, Eric
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Helmholtz-Institut für Pharmazeutische Forschung Saarland, Universitätscampus E8.1,56123 Saarbrücken, Germany.
2016-07-27T13:24:30Z
2016-07-27T13:24:30Z
2016-06-06
Synthesis of a deuterated probe for the confocal Raman microscopy imaging of squalenoyl nanomedicines 2016, 12:1127 Beilstein Journal of Organic Chemistry
1860-5397
10.3762/bjoc.12.109
http://hdl.handle.net/10033/617612
Beilstein Journal of Organic Chemistry
info:eu-repo/grantAgreement/EC/FP7/249835
http://www.beilstein-journals.org/bjoc/content/12/1/109
openAccess
http://creativecommons.org/licenses/by-nc-sa/4.0/
Synthesis of a deuterated probe for the confocal Raman microscopy imaging of squalenoyl nanomedicines
Article
2018-06-13T03:54:50Z
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Helmholtz Zentrum für Infektionsforschung Repository
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oai:repository.helmholtz-hzi.de:10033/6179852019-09-06T01:30:53Zcom_10033_620613col_10033_620614
Mostaghaci, Babak
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Loretz, Brigitta
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Lehr, Claus-Michael
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Helmholtz Institut f?r Pharmazeutische Forschung Saarland, Universit?tscampus E8.1, 66123 Saarbr?cken, Germany.
2016-08-05T13:38:56Z
2016-08-05T13:38:56Z
2016
Calcium Phosphate System for Gene Delivery: Historical Background and Emerging Opportunities. 2016, 22 (11):1529-33 Curr. Pharm. Des.
1873-4286
26654437
http://hdl.handle.net/10033/617985
Current pharmaceutical design
Calcium phosphate system has been used widely in in vitro gene delivery for almost four decades. Excellent biocompatibility and simple application have motivated the researchers to always consider this system in their transfection experiments. However, there was a major drawback regarding the low transfection efficiency of calcium phosphate. Hence, there have been many efforts in order to increase the gene delivery potential of this system. In this paper, the application of calcium phosphate in gene delivery is introduced. Moreover, the recent progresses in the application of calcium phosphate in the delivery of (oligo)nucleotides and different approaches to improve the properties of this system are reviewed.
en
http://creativecommons.org/licenses/by-nc-sa/4.0/
Calcium Phosphate System for Gene Delivery: Historical Background and Emerging Opportunities.
Article
2017-03-01T00:00:00Z
Calcium phosphate system has been used widely in in vitro gene delivery for almost four decades. Excellent biocompatibility and simple application have motivated the researchers to always consider this system in their transfection experiments. However, there was a major drawback regarding the low transfection efficiency of calcium phosphate. Hence, there have been many efforts in order to increase the gene delivery potential of this system. In this paper, the application of calcium phosphate in gene delivery is introduced. Moreover, the recent progresses in the application of calcium phosphate in the delivery of (oligo)nucleotides and different approaches to improve the properties of this system are reviewed.
ORIGINAL
Mostaghaci, Loretz and Lehr.pdf
Mostaghaci, Loretz and Lehr.pdf
original manuscript
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TEXT
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Mostaghaci, Loretz and Lehr.pdf.txt
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2019-09-06 01:30:53.145
Helmholtz Zentrum für Infektionsforschung Repository
hzi@openrepository.com
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oai:repository.helmholtz-hzi.de:10033/6186022019-08-30T11:27:16Zcom_10033_620613col_10033_620614
Planz, Viktoria
39e369d664c0bdd6712c3d972dba5341
500
Seif, Salem
527166ce732ea704fe49ce17fbceed43
500
Atchison, Jennifer S
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500
Vukosavljevic, Branko
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Sparenberg, Lisa
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500
Kroner, Elmar
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Windbergs, Maike
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Helmholtz-Institute for Pharmaceutical Research Saarland (HIPS),Saarland, Universitätscampus E8.1, 66123 Saarbrücken, Germany.
2016-08-19T13:52:06Z
2016-08-19T13:52:06Z
2016-07-11
Three-dimensional hierarchical cultivation of human skin cells on bio-adaptive hybrid fibers. 2016, 8 (7):775-84 Integr Biol (Camb)
1757-9708
27241237
10.1039/c6ib00080k
http://hdl.handle.net/10033/618602
Integrative biology : quantitative biosciences from nano to macro
The human skin comprises a complex multi-scale layered structure with hierarchical organization of different cells within the extracellular matrix (ECM). This supportive fiber-reinforced structure provides a dynamically changing microenvironment with specific topographical, mechanical and biochemical cell recognition sites to facilitate cell attachment and proliferation. Current advances in developing artificial matrices for cultivation of human cells concentrate on surface functionalizing of biocompatible materials with different biomolecules like growth factors to enhance cell attachment. However, an often neglected aspect for efficient modulation of cell-matrix interactions is posed by the mechanical characteristics of such artificial matrices. To address this issue, we fabricated biocompatible hybrid fibers simulating the complex biomechanical characteristics of native ECM in human skin. Subsequently, we analyzed interactions of such fibers with human skin cells focusing on the identification of key fiber characteristics for optimized cell-matrix interactions. We successfully identified the mediating effect of bio-adaptive elasto-plastic stiffness paired with hydrophilic surface properties as key factors for cell attachment and proliferation, thus elucidating the synergistic role of these parameters to induce cellular responses. Co-cultivation of fibroblasts and keratinocytes on such fiber mats representing the specific cells in dermis and epidermis resulted in a hierarchical organization of dermal and epidermal tissue layers. In addition, terminal differentiation of keratinocytes at the air interface was observed. These findings provide valuable new insights into cell behaviour in three-dimensional structures and cell-material interactions which can be used for rational development of bio-inspired functional materials for advanced biomedical applications.
en
http://creativecommons.org/licenses/by-nc-sa/4.0/
Three-dimensional hierarchical cultivation of human skin cells on bio-adaptive hybrid fibers.
Article
2018-06-13T01:37:49Z
The human skin comprises a complex multi-scale layered structure with hierarchical organization of different cells within the extracellular matrix (ECM). This supportive fiber-reinforced structure provides a dynamically changing microenvironment with specific topographical, mechanical and biochemical cell recognition sites to facilitate cell attachment and proliferation. Current advances in developing artificial matrices for cultivation of human cells concentrate on surface functionalizing of biocompatible materials with different biomolecules like growth factors to enhance cell attachment. However, an often neglected aspect for efficient modulation of cell-matrix interactions is posed by the mechanical characteristics of such artificial matrices. To address this issue, we fabricated biocompatible hybrid fibers simulating the complex biomechanical characteristics of native ECM in human skin. Subsequently, we analyzed interactions of such fibers with human skin cells focusing on the identification of key fiber characteristics for optimized cell-matrix interactions. We successfully identified the mediating effect of bio-adaptive elasto-plastic stiffness paired with hydrophilic surface properties as key factors for cell attachment and proliferation, thus elucidating the synergistic role of these parameters to induce cellular responses. Co-cultivation of fibroblasts and keratinocytes on such fiber mats representing the specific cells in dermis and epidermis resulted in a hierarchical organization of dermal and epidermal tissue layers. In addition, terminal differentiation of keratinocytes at the air interface was observed. These findings provide valuable new insights into cell behaviour in three-dimensional structures and cell-material interactions which can be used for rational development of bio-inspired functional materials for advanced biomedical applications.
ORIGINAL
Planz et al.pdf
Planz et al.pdf
Open Access article
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Planz et al.pdf.txt
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Planz supporting info.pdf.txt
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Extracted Text
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THUMBNAIL
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2019-08-30 11:27:16.315
Helmholtz Zentrum für Infektionsforschung Repository
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oai:repository.helmholtz-hzi.de:10033/6206072018-06-12T17:07:04Zcom_10033_620613col_10033_620614
Hittinger, Marius
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Schneider-Daum, Nicole
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Lehr, Claus Michael
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Helmholtz-Institute for Pharmaceutical Research Saarland (HIPS),Saarland 9 University, 66123 Saarbrücken, Germany.
2016-11-29T09:17:27Z
2016-11-29T09:17:27Z
2016-09
Autologous co-culture of primary human alveolar macrophages and epithelial cells for investigating aerosol medicines. Part I: model characterisation. 2016, 44 (4):337-347 Altern Lab Anim
0261-1929
27685185
http://hdl.handle.net/10033/620607
Alternatives to laboratory animals : ATLA
The development of new formulations for pulmonary drug delivery is a challenge on its own. New in vitro models which address the lung are aimed at predicting and optimising the quality, efficacy and safety of inhaled drugs, to facilitate the more rapid translation of such products into the clinic. Reducing the complexity of the in vivo situation requires that such models reproducibly reflect essential physiological factors in vitro. The choice of cell types, culture conditions and the experimental set-up, can affect the outcome and the relevance of a study. In the alveolar space of the lung, epithelial cells and alveolar macrophages are the most important cell types, forming an efficient cellular barrier to aerosols. Our aim was to mimic this barrier with primary human alveolar cells. Cell densities of alveolar macrophages and epithelial cells, isolated from the same human donor, were optimised, with a focus on barrier properties. The combination of 300,000 epithelial cells/cm² together with 100,000 macrophages/cm² showed a functional barrier (transepithelial electrical resistance > 500Ω.cm²). This cell model was combined with the Pharmaceutical Aerosol Deposition Device on Cell Cultures. The functionality of the in vitro system was investigated with spray-dried fluorescently labelled poly(lactic-co-glycolic) acid particles loaded with ovalbumin as a model drug.
ENG
http://creativecommons.org/licenses/by-nc-sa/4.0/
Autologous co-culture of primary human alveolar macrophages and epithelial cells for investigating aerosol medicines. Part I: model characterisation.
Article
2018-06-12T16:44:56Z
The development of new formulations for pulmonary drug delivery is a challenge on its own. New in vitro models which address the lung are aimed at predicting and optimising the quality, efficacy and safety of inhaled drugs, to facilitate the more rapid translation of such products into the clinic. Reducing the complexity of the in vivo situation requires that such models reproducibly reflect essential physiological factors in vitro. The choice of cell types, culture conditions and the experimental set-up, can affect the outcome and the relevance of a study. In the alveolar space of the lung, epithelial cells and alveolar macrophages are the most important cell types, forming an efficient cellular barrier to aerosols. Our aim was to mimic this barrier with primary human alveolar cells. Cell densities of alveolar macrophages and epithelial cells, isolated from the same human donor, were optimised, with a focus on barrier properties. The combination of 300,000 epithelial cells/cm² together with 100,000 macrophages/cm² showed a functional barrier (transepithelial electrical resistance > 500Ω.cm²). This cell model was combined with the Pharmaceutical Aerosol Deposition Device on Cell Cultures. The functionality of the in vitro system was investigated with spray-dried fluorescently labelled poly(lactic-co-glycolic) acid particles loaded with ovalbumin as a model drug.
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Helmholtz Zentrum für Infektionsforschung Repository
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oai:repository.helmholtz-hzi.de:10033/6205792019-08-30T11:26:42Zcom_10033_620613col_10033_620614
Hittinger, Marius
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Scherließ, Regina
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Schneider-Daum, Nicole
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Lehr, Claus Michael
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http://orcid.org/0000-0002-5864-8462
Helmholtz-Institute for Pharmaceutical Research Saarland,Universitätscampus E8.1, 66123 Saarbrücken, Germany.
2016-11-15T13:07:03Z
2016-11-15T13:07:03Z
2016-09
Autologous co-culture of primary human alveolar macrophages and epithelial cells for investigating aerosol medicines. Part I: model characterisation. 2016, 44 (4):337-347 Altern Lab Anim
0261-1929
27685185
http://hdl.handle.net/10033/620579
Alternatives to laboratory animals : ATLA
The development of new formulations for pulmonary drug delivery is a challenge on its own. New in vitro models which address the lung are aimed at predicting and optimising the quality, efficacy and safety of inhaled drugs, to facilitate the more rapid translation of such products into the clinic. Reducing the complexity of the in vivo situation requires that such models reproducibly reflect essential physiological factors in vitro. The choice of cell types, culture conditions and the experimental set-up, can affect the outcome and the relevance of a study. In the alveolar space of the lung, epithelial cells and alveolar macrophages are the most important cell types, forming an efficient cellular barrier to aerosols. Our aim was to mimic this barrier with primary human alveolar cells. Cell densities of alveolar macrophages and epithelial cells, isolated from the same human donor, were optimised, with a focus on barrier properties. The combination of 300,000 epithelial cells/cm² together with 100,000 macrophages/cm² showed a functional barrier (transepithelial electrical resistance > 500Ω.cm²). This cell model was combined with the Pharmaceutical Aerosol Deposition Device on Cell Cultures. The functionality of the in vitro system was investigated with spray-dried fluorescently labelled poly(lactic-co-glycolic) acid particles loaded with ovalbumin as a model drug.
ENG
en
http://creativecommons.org/licenses/by-nc-sa/4.0/
Autologous co-culture of primary human alveolar macrophages and epithelial cells for investigating aerosol medicines. Part I: model characterisation.
Article
2018-06-13T16:58:37Z
The development of new formulations for pulmonary drug delivery is a challenge on its own. New in vitro models which address the lung are aimed at predicting and optimising the quality, efficacy and safety of inhaled drugs, to facilitate the more rapid translation of such products into the clinic. Reducing the complexity of the in vivo situation requires that such models reproducibly reflect essential physiological factors in vitro. The choice of cell types, culture conditions and the experimental set-up, can affect the outcome and the relevance of a study. In the alveolar space of the lung, epithelial cells and alveolar macrophages are the most important cell types, forming an efficient cellular barrier to aerosols. Our aim was to mimic this barrier with primary human alveolar cells. Cell densities of alveolar macrophages and epithelial cells, isolated from the same human donor, were optimised, with a focus on barrier properties. The combination of 300,000 epithelial cells/cm² together with 100,000 macrophages/cm² showed a functional barrier (transepithelial electrical resistance > 500Ω.cm²). This cell model was combined with the Pharmaceutical Aerosol Deposition Device on Cell Cultures. The functionality of the in vitro system was investigated with spray-dried fluorescently labelled poly(lactic-co-glycolic) acid particles loaded with ovalbumin as a model drug.
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Helmholtz Zentrum für Infektionsforschung Repository
hzi@openrepository.com
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oai:repository.helmholtz-hzi.de:10033/6205802019-08-30T11:26:42Zcom_10033_620613col_10033_620614
Hittinger, Marius
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Mell, Nico Alexander
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Huwer, Hanno
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Loretz, Brigitta
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Schneider-Daum, Nicole
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Lehr, Claus Michael
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http://orcid.org/0000-0002-5864-8462
Helmholtz-Institute for Pharmaceutical Research Saarland,Universitätscampus E8.1, 66123 Saarbrücken, Germany.
2016-11-15T13:09:07Z
2016-11-15T13:09:07Z
2016-09
Autologous co-culture of primary human alveolar macrophages and epithelial cells for investigating aerosol medicines. Part II: evaluation of IL-10-loaded microparticles for the treatment of lung inflammation. 2016, 44 (4):349-360 Altern Lab Anim
0261-1929
27685186
http://hdl.handle.net/10033/620580
Alternatives to laboratory animals : ATLA
Acute respiratory distress syndrome is linked to inflammatory processes in the human lung. The aim of this study was to mimic in vitro the treatment of lung inflammation by using a cell-based human autologous co-culture model. As a potential trial medication, we developed a pulmonary dry powder formulation loaded with interleukin-10 (IL-10), a potent anti-inflammatory cytokine. The inflammatory immune response was stimulated by lipopolysaccharide. The co-culture was combined with the Pharmaceutical Aerosol Deposition Device on Cell Cultures )PADDOCC), to deposit the IL-10-loaded microparticles on the inflamed co-culture model at the air-liquid interface. This treatment significantly reduced the secretion of interleukin-6 and tumour necrosis factor, as compared to the deposition of placebo (unloaded) particles. Our results show that the alveolar co-culture model, in combination with a deposition device such as the PADDOCC, may serve as a powerful tool for testing the safety and efficacy of dry powder formulations for pulmonary drug delivery.
ENG
en
http://creativecommons.org/licenses/by-nc-sa/4.0/
Autologous co-culture of primary human alveolar macrophages and epithelial cells for investigating aerosol medicines. Part II: evaluation of IL-10-loaded microparticles for the treatment of lung inflammation.
Article
2018-06-12T22:02:58Z
Acute respiratory distress syndrome is linked to inflammatory processes in the human lung. The aim of this study was to mimic in vitro the treatment of lung inflammation by using a cell-based human autologous co-culture model. As a potential trial medication, we developed a pulmonary dry powder formulation loaded with interleukin-10 (IL-10), a potent anti-inflammatory cytokine. The inflammatory immune response was stimulated by lipopolysaccharide. The co-culture was combined with the Pharmaceutical Aerosol Deposition Device on Cell Cultures )PADDOCC), to deposit the IL-10-loaded microparticles on the inflamed co-culture model at the air-liquid interface. This treatment significantly reduced the secretion of interleukin-6 and tumour necrosis factor, as compared to the deposition of placebo (unloaded) particles. Our results show that the alveolar co-culture model, in combination with a deposition device such as the PADDOCC, may serve as a powerful tool for testing the safety and efficacy of dry powder formulations for pulmonary drug delivery.
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2019-08-30 11:26:42.759
Helmholtz Zentrum für Infektionsforschung Repository
hzi@openrepository.com
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oai:repository.helmholtz-hzi.de:10033/6205822019-08-30T11:26:13Zcom_10033_620613col_10033_620614
Lerner, Thomas R
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de Souza Carvalho-Wodarz, Cristiane
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Repnik, Urska
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Russell, Matthew R G
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Borel, Sophie
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Diedrich, Collin R
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Rohde, M
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http://orcid.org/0000-0003-0522-3580
Wainwright, Helen
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Collinson, Lucy M
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Wilkinson, Robert J
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Griffiths, Gareth
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Gutierrez, Maximiliano G
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Helmholtz-Institute for Pharmaceutical Research Saarland (HIPS),Saarland Universitätscampus E8.1, 66123 Saarbrücken, Germany.
2016-11-17T08:52:31Z
2016-11-17T08:52:31Z
2016-03-01
Lymphatic endothelial cells are a replicative niche for Mycobacterium tuberculosis. 2016, 126 (3):1093-108 J. Clin. Invest.
1558-8238
26901813
10.1172/JCI83379
http://hdl.handle.net/10033/620582
The Journal of clinical investigation
In extrapulmonary tuberculosis, the most common site of infection is within the lymphatic system, and there is growing recognition that lymphatic endothelial cells (LECs) are involved in immune function. Here, we identified LECs, which line the lymphatic vessels, as a niche for Mycobacterium tuberculosis in the lymph nodes of patients with tuberculosis. In cultured primary human LECs (hLECs), we determined that M. tuberculosis replicates both in the cytosol and within autophagosomes, but the bacteria failed to replicate when the virulence locus RD1 was deleted. Activation by IFN-γ induced a cell-autonomous response in hLECs via autophagy and NO production that restricted M. tuberculosis growth. Thus, depending on the activation status of LECs, autophagy can both promote and restrict replication. Together, these findings reveal a previously unrecognized role for hLECs and autophagy in tuberculosis pathogenesis and suggest that hLECs are a potential niche for M. tuberculosis that allows establishment of persistent infection in lymph nodes.
ENG
info:eu-repo/grantAgreement/EC/FP7/289454
openAccess
http://creativecommons.org/licenses/by-nc-sa/4.0/
Autophagy
Cells, Cultured
Endothelial Cells
Granuloma
Humans
Lymph Nodes
Mycobacterium tuberculosis
Nitric Oxide
Tuberculosis
Lymphatic endothelial cells are a replicative niche for Mycobacterium tuberculosis.
Article
2018-06-13T03:42:49Z
In extrapulmonary tuberculosis, the most common site of infection is within the lymphatic system, and there is growing recognition that lymphatic endothelial cells (LECs) are involved in immune function. Here, we identified LECs, which line the lymphatic vessels, as a niche for Mycobacterium tuberculosis in the lymph nodes of patients with tuberculosis. In cultured primary human LECs (hLECs), we determined that M. tuberculosis replicates both in the cytosol and within autophagosomes, but the bacteria failed to replicate when the virulence locus RD1 was deleted. Activation by IFN-γ induced a cell-autonomous response in hLECs via autophagy and NO production that restricted M. tuberculosis growth. Thus, depending on the activation status of LECs, autophagy can both promote and restrict replication. Together, these findings reveal a previously unrecognized role for hLECs and autophagy in tuberculosis pathogenesis and suggest that hLECs are a potential niche for M. tuberculosis that allows establishment of persistent infection in lymph nodes.
ORIGINAL
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2019-08-30 11:26:13.139
Helmholtz Zentrum für Infektionsforschung Repository
hzi@openrepository.com
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oai:repository.helmholtz-hzi.de:10033/6206152019-08-30T11:35:39Zcom_10033_620613col_10033_620614
Thiele, Carolin
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Loretz, Brigitta
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Lehr, Claus Michael
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http://orcid.org/0000-0002-5864-8462
Helmholtz-Institute for Pharmaceutical Research Saarland (HIPS),Saarland Universitätscampus E8.1, 66123 Saarbrücken, Germany.
2016-12-01T09:22:46Z
2016-12-01T09:22:46Z
2016-10-03
Biodegradable starch derivatives with tunable charge density-synthesis, characterization, and transfection efficiency. 2016: Drug Deliv Transl Res
2190-3948
27699593
10.1007/s13346-016-0333-8
http://hdl.handle.net/10033/620615
Drug delivery and translational research
Regioselective oxidation of water-soluble starch and conversion with alkyl diamines resulted in defined cationic starch derivatives. Those were assessed in their potential for polyplex formation, biocompatibility, and transfection efficacy. The new polymers have the advantage of being biodegradable, being not cytotoxic at rather high concentrations (LC50 > 400 μg/ml) for C2 substitution, and reach transfection efficiencies comparable to commercial transfection reagents. The polymer with the highest transfection efficacy is a C12 substituted polymer (degree of substitution = 30 %) at N/P 3. The LC50 value of that highly modified polymer is still one order of magnitude lower than that of PEI 25 kDa.
ENG
http://creativecommons.org/licenses/by-nc-sa/4.0/
Biodegradable starch derivatives with tunable charge density-synthesis, characterization, and transfection efficiency.
Article
2017-10-03T00:00:00Z
Regioselective oxidation of water-soluble starch and conversion with alkyl diamines resulted in defined cationic starch derivatives. Those were assessed in their potential for polyplex formation, biocompatibility, and transfection efficacy. The new polymers have the advantage of being biodegradable, being not cytotoxic at rather high concentrations (LC50 > 400 μg/ml) for C2 substitution, and reach transfection efficiencies comparable to commercial transfection reagents. The polymer with the highest transfection efficacy is a C12 substituted polymer (degree of substitution = 30 %) at N/P 3. The LC50 value of that highly modified polymer is still one order of magnitude lower than that of PEI 25 kDa.
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Helmholtz Zentrum für Infektionsforschung Repository
hzi@openrepository.com
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oai:repository.helmholtz-hzi.de:10033/6208762019-08-30T11:35:39Zcom_10033_620613col_10033_620614
Susewind, Julia
a8e317ab96ed4a00f62d3eb96dc3e2c5
500
de Souza Carvalho-Wodarz, Cristiane
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500
Repnik, Urska
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Collnot, Eva-Maria
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Schneider-Daum, Nicole
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Griffiths, Gareth Wyn
99db8acdd2f6c11e2f9909fb41751beb
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Lehr, Claus-Michael
e25b30ba80302580419199334c0f4c6b
500
Helmholtz-Institut für Pharmaceutische Forschung Saarland, Universitätscampus E8.1, 66123 Saarbrücken, Germany.
2017-03-29T12:57:20Z
2017-03-29T12:57:20Z
2016
A 3D co-culture of three human cell lines to model the inflamed intestinal mucosa for safety testing of nanomaterials. 2016, 10 (1):53-62 Nanotoxicology
1743-5404
25738417
10.3109/17435390.2015.1008065
http://hdl.handle.net/10033/620876
Nanotoxicology
Oral exposure to nanomaterials is a current concern, asking for innovative biological test systems to assess their safety, especially also in conditions of inflammatory disorders. Aim of this study was to develop a 3D intestinal model, consisting of Caco-2 cells and two human immune cell lines, suitable to assess nanomaterial toxicity, in either healthy or diseased conditions. Human macrophages (THP-1) and human dendritic cells (MUTZ-3) were embedded in a collagen scaffold and seeded on the apical side of transwell inserts. Caco-2 cells were seeded on top of this layer, forming a 3D model of the intestinal mucosa. Toxicity of engineered nanoparticles (NM101 TiO2, NM300 Ag, Au) was evaluated in non-inflamed and inflamed co-cultures, and also compared to non-inflamed Caco-2 monocultures. Inflammation was elicited by IL-1β, and interactions with engineered NPs were addressed by different endpoints. The 3D co-culture showed well preserved ultrastructure and significant barrier properties. Ag NPs were found to be more toxic than TiO2 or Au NPs. But once inflamed with IL-1β, the co-cultures released higher amounts of IL-8 compared to Caco-2 monocultures. However, the cytotoxicity of Ag NPs was higher in Caco-2 monocultures than in 3D co-cultures. The naturally higher IL-8 production in the co-cultures was enhanced even further by the Ag NPs. This study shows that it is possible to mimic inflamed conditions in a 3D co-culture model of the intestinal mucosa. The fact that it is based on three easily available human cell lines makes this model valuable to study the safety of nanomaterials in the context of inflammation.
en
info:eu-repo/grantAgreement/EC/FP7/ 228625
openAccess
http://creativecommons.org/licenses/by-nc-sa/4.0/
Caco-2 Cells
Coculture Techniques
Humans
Inflammation
Interleukin-8
Intestinal Mucosa
Metal Nanoparticles
Nanostructures
Titanium
A 3D co-culture of three human cell lines to model the inflamed intestinal mucosa for safety testing of nanomaterials.
Article
2018-06-12T17:34:53Z
Oral exposure to nanomaterials is a current concern, asking for innovative biological test systems to assess their safety, especially also in conditions of inflammatory disorders. Aim of this study was to develop a 3D intestinal model, consisting of Caco-2 cells and two human immune cell lines, suitable to assess nanomaterial toxicity, in either healthy or diseased conditions. Human macrophages (THP-1) and human dendritic cells (MUTZ-3) were embedded in a collagen scaffold and seeded on the apical side of transwell inserts. Caco-2 cells were seeded on top of this layer, forming a 3D model of the intestinal mucosa. Toxicity of engineered nanoparticles (NM101 TiO2, NM300 Ag, Au) was evaluated in non-inflamed and inflamed co-cultures, and also compared to non-inflamed Caco-2 monocultures. Inflammation was elicited by IL-1β, and interactions with engineered NPs were addressed by different endpoints. The 3D co-culture showed well preserved ultrastructure and significant barrier properties. Ag NPs were found to be more toxic than TiO2 or Au NPs. But once inflamed with IL-1β, the co-cultures released higher amounts of IL-8 compared to Caco-2 monocultures. However, the cytotoxicity of Ag NPs was higher in Caco-2 monocultures than in 3D co-cultures. The naturally higher IL-8 production in the co-cultures was enhanced even further by the Ag NPs. This study shows that it is possible to mimic inflamed conditions in a 3D co-culture model of the intestinal mucosa. The fact that it is based on three easily available human cell lines makes this model valuable to study the safety of nanomaterials in the context of inflammation.
ORIGINAL
Susewind et al.pdf
Susewind et al.pdf
free Research Gate Net PDF
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Helmholtz Zentrum für Infektionsforschung Repository
hzi@openrepository.com
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Helmholtz-Institute for Pharmaceutical Research Saarland (HIPS),Saarland 9 University, 66123 Saarbrücken, Germany.
2017-04-06T09:35:04Z
2017-04-06T09:35:04Z
2017-03-28
Diverse Applications of Nanomedicine. 2017, 11 (3):2313-2381 ACS Nano
1936-086X
28290206
10.1021/acsnano.6b06040
http://hdl.handle.net/10033/620887
ACS nano
The design and use of materials in the nanoscale size range for addressing medical and health-related issues continues to receive increasing interest. Research in nanomedicine spans a multitude of areas, including drug delivery, vaccine development, antibacterial, diagnosis and imaging tools, wearable devices, implants, high-throughput screening platforms, etc. using biological, nonbiological, biomimetic, or hybrid materials. Many of these developments are starting to be translated into viable clinical products. Here, we provide an overview of recent developments in nanomedicine and highlight the current challenges and upcoming opportunities for the field and translation to the clinic.
en
http://creativecommons.org/licenses/by-nc-sa/4.0/
Diverse Applications of Nanomedicine.
Article
2018-06-13T21:33:41Z
The design and use of materials in the nanoscale size range for addressing medical and health-related issues continues to receive increasing interest. Research in nanomedicine spans a multitude of areas, including drug delivery, vaccine development, antibacterial, diagnosis and imaging tools, wearable devices, implants, high-throughput screening platforms, etc. using biological, nonbiological, biomimetic, or hybrid materials. Many of these developments are starting to be translated into viable clinical products. Here, we provide an overview of recent developments in nanomedicine and highlight the current challenges and upcoming opportunities for the field and translation to the clinic.
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2019-08-30 11:36:04.935
Helmholtz Zentrum für Infektionsforschung Repository
hzi@openrepository.com
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oai:repository.helmholtz-hzi.de:10033/6209242019-08-30T11:33:57Zcom_10033_620613col_10033_620614
Günday Türeli, Nazende
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Helmholtz-Institut für Pharmazeutische Forschung Saarland, Universitätscampus E8.1, 66123 Saarbrücken, Germany.
2017-05-18T13:18:24Z
2017-05-18T13:18:24Z
2017-05-02
Ciprofloxacin-loaded PLGA nanoparticles against Cystic Fibrosis P. aeruginosa Lung Infections. 2017 Eur J Pharm Biopharm
1873-3441
28476373
10.1016/j.ejpb.2017.04.032
http://hdl.handle.net/10033/620924
European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V
Current pulmonary treatments against Pseudomonasaeruginosa infections in cystic fibrosis (CF) lung suffer from deactivation of the drug and immobilization in thick and viscous biofilm/mucus blend, along with the general antibiotic resistance. Administration of nanoparticles (NPs) with high antibiotic load capable of penetrating the tight mesh of biofilm/mucus can be an advent to overcome the treatment bottlenecks. Biodegradable and biocompatible polymer nanoparticles efficiently loaded with ciprofloxacin complex offer a solution for emerging treatment strategies. NPs were prepared under controlled conditions by utilizing MicroJet Reactor (MJR) to yield a particle size of 190.4±28.6 nm with 0.089 PDI. Encapsulation efficiency of the drug was 79% resulting in a loading of 14%. Release was determined to be controlled and medium-independent in PBS, PBS+0.2% Tween 80 and simulated lung fluid. Cytotoxicity assays with Calu3 cells and CF bronchial epithelial cells (CFBE41o(-)) indicated that complex loaded PLGA NPs were non-toxic at concentrations >MICcipro against lab strains of the bacteria. Antibacterial activity tests revealed enhanced activity when applied as nanoparticles. NPs' colloidal stability in mucus was proven. Notably, a decrease in mucus turbidity was observed upon incubation with NPs. Herewith, ciprofloxacin complex loaded PLGA NPs are introduced as promising pulmonary nano drug delivery systems against P.aeruginosa infections in CF lung.
en
http://creativecommons.org/licenses/by-nc-sa/4.0/
Ciprofloxacin-loaded PLGA nanoparticles against Cystic Fibrosis P. aeruginosa Lung Infections.
Article
2018-08-15T00:00:00Z
Current pulmonary treatments against Pseudomonasaeruginosa infections in cystic fibrosis (CF) lung suffer from deactivation of the drug and immobilization in thick and viscous biofilm/mucus blend, along with the general antibiotic resistance. Administration of nanoparticles (NPs) with high antibiotic load capable of penetrating the tight mesh of biofilm/mucus can be an advent to overcome the treatment bottlenecks. Biodegradable and biocompatible polymer nanoparticles efficiently loaded with ciprofloxacin complex offer a solution for emerging treatment strategies. NPs were prepared under controlled conditions by utilizing MicroJet Reactor (MJR) to yield a particle size of 190.4±28.6 nm with 0.089 PDI. Encapsulation efficiency of the drug was 79% resulting in a loading of 14%. Release was determined to be controlled and medium-independent in PBS, PBS+0.2% Tween 80 and simulated lung fluid. Cytotoxicity assays with Calu3 cells and CF bronchial epithelial cells (CFBE41o(-)) indicated that complex loaded PLGA NPs were non-toxic at concentrations >MICcipro against lab strains of the bacteria. Antibacterial activity tests revealed enhanced activity when applied as nanoparticles. NPs' colloidal stability in mucus was proven. Notably, a decrease in mucus turbidity was observed upon incubation with NPs. Herewith, ciprofloxacin complex loaded PLGA NPs are introduced as promising pulmonary nano drug delivery systems against P.aeruginosa infections in CF lung.
ORIGINAL
Türeli et al.pdf
Türeli et al.pdf
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2019-08-30 11:33:57.305
Helmholtz Zentrum für Infektionsforschung Repository
hzi@openrepository.com
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oai:repository.helmholtz-hzi.de:10033/6209262019-08-30T11:35:39Zcom_10033_620613col_10033_620614
Nickel, Sabrina
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500
Selo, Mohammed Ali
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Fallack, Juliane
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Clerkin, Caoimhe G
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Huwer, Hanno
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Schneider-Daum, Nicole
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Lehr, Claus Michael
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http://orcid.org/0000-0002-5864-8462
Ehrhardt, Carsten
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Helmholtz Institut für Pharmaceutischr Forschung Saarland, Universitätscampus E8.1, 66123 Saarbrücken, Germany.
2017-05-22T11:54:26Z
2017-05-22T11:54:26Z
2017-05-03
Expression and Activity of Breast Cancer Resistance Protein (BCRP/ABCG2) in Human Distal Lung Epithelial Cells In Vitro. 2017 Pharm. Res.
1573-904X
28470471
10.1007/s11095-017-2172-9
http://hdl.handle.net/10033/620926
Pharmaceutical research
Breast cancer resistance protein (BCRP/ABCG2) has previously been identified with high expression levels in human lung. The subcellular localisation and functional activity of the transporter in lung epithelia, however, remains poorly investigated. The aim of this project was to study BCRP expression and activity in freshly isolated human alveolar epithelial type 2 (AT2) and type 1-like (AT1-like) cells in primary culture, and to compare these findings with data obtained from the NCI-H441 cell line.
en
http://creativecommons.org/licenses/by-nc-sa/4.0/
Expression and Activity of Breast Cancer Resistance Protein (BCRP/ABCG2) in Human Distal Lung Epithelial Cells In Vitro.
Article
2018-05-05T00:00:00Z
Breast cancer resistance protein (BCRP/ABCG2) has previously been identified with high expression levels in human lung. The subcellular localisation and functional activity of the transporter in lung epithelia, however, remains poorly investigated. The aim of this project was to study BCRP expression and activity in freshly isolated human alveolar epithelial type 2 (AT2) and type 1-like (AT1-like) cells in primary culture, and to compare these findings with data obtained from the NCI-H441 cell line.
ORIGINAL
Nickel_BCRP resubmission.pdf
Nickel_BCRP resubmission.pdf
original manuscript
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Helmholtz Zentrum für Infektionsforschung Repository
hzi@openrepository.com
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oai:repository.helmholtz-hzi.de:10033/6209322019-08-30T11:33:05Zcom_10033_620613col_10033_620614
Ricci, Francesca
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500
Murgia, Xabier
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Razzetti, Roberta
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Pelizzi, Nicola
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Salomone, Fabrizio
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Helmholtz Institut für pharmazeutische Forschung Saarland, Universitätscampus E8.1, 66123 Saarbrücken, Germany.
2017-06-01T09:23:41Z
2017-06-01T09:23:41Z
2017-02
In vitro and in vivo comparison between poractant alfa and the new generation synthetic surfactant CHF5633. 2017, 81 (2):369-375 Pediatr. Res.
1530-0447
27973472
10.1038/pr.2016.231
http://hdl.handle.net/10033/620932
Pediatric research
CHF5633 is a new generation synthetic surfactant containing both SP-B and SP-C analogues developed for the treatment of respiratory distress syndrome. Here, the optimal dose and its performance in comparison to the animal-derived surfactant poractant alfa were investigated.
en
http://creativecommons.org/licenses/by-nc-sa/4.0/
In vitro and in vivo comparison between poractant alfa and the new generation synthetic surfactant CHF5633.
Article
2017-08-01T00:00:00Z
CHF5633 is a new generation synthetic surfactant containing both SP-B and SP-C analogues developed for the treatment of respiratory distress syndrome. Here, the optimal dose and its performance in comparison to the animal-derived surfactant poractant alfa were investigated.
ORIGINAL
Ricci et al.pdf
Ricci et al.pdf
original manuscript
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Ricci et al.pdf.jpg
Ricci et al.pdf.jpg
Generated Thumbnail
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Helmholtz Zentrum für Infektionsforschung Repository
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oai:repository.helmholtz-hzi.de:10033/6210122019-08-30T11:25:43Zcom_10033_620613col_10033_620614
Ricci, Francesca
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Catozzi, Chiara
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Murgia, Xabier
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Rosa, Brenda
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Amidani, Davide
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Lorenzini, Luca
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Bianco, Federico
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Rivetti, Claudio
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Catinella, Silvia
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Villetti, Gino
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Civelli, Maurizio
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Pioselli, Barbara
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Dani, Carlo
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Salomone, Fabrizio
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Helmholtz-Institut für Pharmazeutische Forschung Saarland, Universitätscampus E8.1, 66123 Saarbrücken, Germany.
2017-07-14T12:02:37Z
2017-07-14T12:02:37Z
2017
Physiological, Biochemical, and Biophysical Characterization of the Lung-Lavaged Spontaneously-Breathing Rabbit as a Model for Respiratory Distress Syndrome. 2017, 12 (1):e0169190 PLoS ONE
1932-6203
28060859
10.1371/journal.pone.0169190
http://hdl.handle.net/10033/621012
PloS one
Nasal continuous positive airway pressure (nCPAP) is a widely accepted technique of non-invasive respiratory support in spontaneously-breathing premature infants with respiratory distress syndrome (RDS). Surfactant administration techniques compatible with nCPAP ventilation strategy are actively investigated. Our aim is to set up and validate a respiratory distress animal model that can be managed on nCPAP suitable for surfactant administration techniques studies. Surfactant depletion was induced by bronchoalveolar lavages (BALs) on 18 adult rabbits. Full depletion was assessed by surfactant component analysis on the BALs samples. Animals were randomized into two groups: Control group (nCPAP only) and InSurE group, consisting of a bolus of surfactant (Poractant alfa, 200 mg/kg) followed by nCPAP. Arterial blood gases were monitored until animal sacrifice, 3 hours post treatment. Lung mechanics were evaluated just before and after BALs, at the time of treatment, and at the end of the procedure. Surfactant phospholipids and protein analysis as well as surface tension measurements on sequential BALs confirmed the efficacy of the surfactant depletion procedure. The InSurE group showed a significant improvement of blood oxygenation and lung mechanics. On the contrary, no signs of recovery were appreciated in animals treated with just nCPAP. The surfactant-depleted adult rabbit RDS model proved to be a valuable and efficient preclinical tool for mimicking the clinical scenario of preterm infants affected by mild/moderate RDS who spontaneously breathe and do not require mechanical ventilation. This population is of particular interest as potential target for the non-invasive administration of surfactant.
en
http://creativecommons.org/licenses/by-nc-sa/4.0/
Physiological, Biochemical, and Biophysical Characterization of the Lung-Lavaged Spontaneously-Breathing Rabbit as a Model for Respiratory Distress Syndrome.
Article
2018-06-12T22:29:52Z
Nasal continuous positive airway pressure (nCPAP) is a widely accepted technique of non-invasive respiratory support in spontaneously-breathing premature infants with respiratory distress syndrome (RDS). Surfactant administration techniques compatible with nCPAP ventilation strategy are actively investigated. Our aim is to set up and validate a respiratory distress animal model that can be managed on nCPAP suitable for surfactant administration techniques studies. Surfactant depletion was induced by bronchoalveolar lavages (BALs) on 18 adult rabbits. Full depletion was assessed by surfactant component analysis on the BALs samples. Animals were randomized into two groups: Control group (nCPAP only) and InSurE group, consisting of a bolus of surfactant (Poractant alfa, 200 mg/kg) followed by nCPAP. Arterial blood gases were monitored until animal sacrifice, 3 hours post treatment. Lung mechanics were evaluated just before and after BALs, at the time of treatment, and at the end of the procedure. Surfactant phospholipids and protein analysis as well as surface tension measurements on sequential BALs confirmed the efficacy of the surfactant depletion procedure. The InSurE group showed a significant improvement of blood oxygenation and lung mechanics. On the contrary, no signs of recovery were appreciated in animals treated with just nCPAP. The surfactant-depleted adult rabbit RDS model proved to be a valuable and efficient preclinical tool for mimicking the clinical scenario of preterm infants affected by mild/moderate RDS who spontaneously breathe and do not require mechanical ventilation. This population is of particular interest as potential target for the non-invasive administration of surfactant.
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oai:hzi.openrepository.com:10033/621012
2019-08-30 11:25:43.444
Helmholtz Zentrum für Infektionsforschung Repository
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oai:repository.helmholtz-hzi.de:10033/6210142019-08-30T11:34:22Zcom_10033_620613col_10033_620614
Rigo, Lucas A
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Carvalho-Wodarz, Cristiane S
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Pohlmann, Adriana R
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Guterres, Silvia S
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Schneider-Daum, Nicole
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Lehr, Claus Michael
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http://orcid.org/0000-0002-5864-8462
Beck, Ruy C R
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Helmholtz-Institut für Pharmazeutische Forschung Saarland [HIPS], Universitätscampus E8.1, 66123 Saarbrücken, Germany.
2017-07-19T10:54:57Z
2017-07-19T10:54:57Z
2017-05-13
Nanoencapsulation of a glucocorticoid improves barrier function and anti-inflammatory effect on monolayers of pulmonary epithelial cell lines. 2017 Eur J Pharm Biopharm
1873-3441
28512018
10.1016/j.ejpb.2017.05.006
http://hdl.handle.net/10033/621014
European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V
The anti-inflammatory effect of polymeric deflazacort nanocapsules (NC-DFZ) was investigated, and possible improvement of epithelial barrier function using filter grown monolayers of A549 and Calu-3 using as models was assessed. NC prepared from poly(ε-caprolactone) (PCL) had a mean size around 200 nm, slightly negative zeta potential (∼ - 8 mV), and low polydispersity index (< 0.10). Encapsulation of DFZ had an efficiency of 85%. No cytotoxic effects were observed at particle concentration of 9.85 x 10(11) NC/ml, which was therefore chosen to evaluate the effect of NC-DFZ at 1% (w/v) of PCL and 0.5% (w/v) of DFZ on the epithelial barrier function of Calu-3 monolayers. Nanoencapsulated drug at 0.5% (w/v) increased transepithelial electrical resistance and decrease permeability of the paracellular marker sodium fluorescein, while non-encapsulated DFZ failed to improve these parameters. Moreover, NC-DFZ reduced the lipopolysaccharide (LPS) mediated secretion of the inflammatory marker IL-8. In vitro dissolution testing revealed controlled release of DFZ from nanocapsules, which may explain the improved effect of DFZ on the cells. These data suggest that nanoencapsulation of pulmonary delivered corticosteroids could be advantageous for the treatment of inflammatory conditions, such as asthma and chronic obstructive pulmonary diseases.
en
http://creativecommons.org/licenses/by-nc-sa/4.0/
Nanoencapsulation of a glucocorticoid improves barrier function and anti-inflammatory effect on monolayers of pulmonary epithelial cell lines.
Article
2018-10-15T00:00:00Z
The anti-inflammatory effect of polymeric deflazacort nanocapsules (NC-DFZ) was investigated, and possible improvement of epithelial barrier function using filter grown monolayers of A549 and Calu-3 using as models was assessed. NC prepared from poly(ε-caprolactone) (PCL) had a mean size around 200 nm, slightly negative zeta potential (∼ - 8 mV), and low polydispersity index (< 0.10). Encapsulation of DFZ had an efficiency of 85%. No cytotoxic effects were observed at particle concentration of 9.85 x 10(11) NC/ml, which was therefore chosen to evaluate the effect of NC-DFZ at 1% (w/v) of PCL and 0.5% (w/v) of DFZ on the epithelial barrier function of Calu-3 monolayers. Nanoencapsulated drug at 0.5% (w/v) increased transepithelial electrical resistance and decrease permeability of the paracellular marker sodium fluorescein, while non-encapsulated DFZ failed to improve these parameters. Moreover, NC-DFZ reduced the lipopolysaccharide (LPS) mediated secretion of the inflammatory marker IL-8. In vitro dissolution testing revealed controlled release of DFZ from nanocapsules, which may explain the improved effect of DFZ on the cells. These data suggest that nanoencapsulation of pulmonary delivered corticosteroids could be advantageous for the treatment of inflammatory conditions, such as asthma and chronic obstructive pulmonary diseases.
ORIGINAL
Rigo et al. 2016 submitted version.pdf
Rigo et al. 2016 submitted version.pdf
original manuscript
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Rigo et al. 2016 submitted version.pdf.txt
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Helmholtz Zentrum für Infektionsforschung Repository
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oai:repository.helmholtz-hzi.de:10033/6210782019-08-30T11:31:22Zcom_10033_620613col_10033_620614
Loretz, Brigitta
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Windbergs, Maike
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Schaefer, Ulrich
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Schneider, Marc
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Lehr, Claus Michael
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HIPS, Helmholtz-Institut für pharmazeutische Forschung Saarland, Universitätscampus E8.1,66123 Saarbrücken, Germany.
2017-08-29T09:32:31Z
2017-08-29T09:32:31Z
2017-09
Barriers and motivations for non-invasive drug delivery. 2017, 118:1-2 Eur J Pharm Biopharm
1873-3441
28433785
10.1016/j.ejpb.2017.04.016
http://hdl.handle.net/10033/621078
European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V
Editorial anlässlich der Special Issue zu unserer BioBarriers Konferenz von 2016.
en
http://creativecommons.org/licenses/by-nc-sa/4.0/
Barriers and motivations for non-invasive drug delivery.
Editorial
2018-09-15T00:00:00Z
ORIGINAL
Loretz et al.pdf
Loretz et al.pdf
original manuscript
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LICENSE
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oai:hzi.openrepository.com:10033/621078
2019-08-30 11:31:22.281
Helmholtz Zentrum für Infektionsforschung Repository
hzi@openrepository.com
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oai:repository.helmholtz-hzi.de:10033/6211432019-08-30T11:34:48Zcom_10033_620613col_10033_620614
Ribeiro, Giovanni Monteiro
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Real, Fernando
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Teixeira, Daniela
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Duarte, Rafael Silva
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Mortara, Renato Arruda
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Leão, Sylvia Cardoso
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de Souza Carvalho-Wodarz, Cristiane
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Helmholtz-Institute for Pharmaceutical Research Saarland (HIPS), Universitycampus E8.1, 66123 Saarbrücken, Germany.
2017-10-24T08:43:03Z
2017-10-24T08:43:03Z
2017-09-13
Increased survival and proliferation of the epidemic strain Mycobacterium abscessus subsp. massiliense CRM0019 in alveolar epithelial cells. 2017, 17 (1):195 BMC Microbiol.
1471-2180
28903728
10.1186/s12866-017-1102-7
http://hdl.handle.net/10033/621143
BMC microbiology
Outbreaks of infections caused by rapidly growing mycobacteria have been reported worldwide generally associated with medical procedures. Mycobacterium abscessus subsp. massiliense CRM0019 was obtained during an epidemic of postsurgical infections and was characterized by increased persistence in vivo. To better understand the successful survival strategies of this microorganism, we evaluated its infectivity and proliferation in macrophages (RAW and BMDM) and alveolar epithelial cells (A549). For that, we assessed the following parameters, for both M. abscessus CRM0019 as well as the reference strain M. abscessus ATCC 19977: internalization, intracellular survival for up 3 days, competence to subvert lysosome fusion and the intracellular survival after cell reinfection.
en
http://creativecommons.org/licenses/by-nc-sa/4.0/
Increased survival and proliferation of the epidemic strain Mycobacterium abscessus subsp. massiliense CRM0019 in alveolar epithelial cells.
Article
2018-06-12T23:39:29Z
Outbreaks of infections caused by rapidly growing mycobacteria have been reported worldwide generally associated with medical procedures. Mycobacterium abscessus subsp. massiliense CRM0019 was obtained during an epidemic of postsurgical infections and was characterized by increased persistence in vivo. To better understand the successful survival strategies of this microorganism, we evaluated its infectivity and proliferation in macrophages (RAW and BMDM) and alveolar epithelial cells (A549). For that, we assessed the following parameters, for both M. abscessus CRM0019 as well as the reference strain M. abscessus ATCC 19977: internalization, intracellular survival for up 3 days, competence to subvert lysosome fusion and the intracellular survival after cell reinfection.
ORIGINAL
Ribeiro et al.pdf
Ribeiro et al.pdf
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THUMBNAIL
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2019-08-30 11:34:48.191
Helmholtz Zentrum für Infektionsforschung Repository
hzi@openrepository.com
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oai:repository.helmholtz-hzi.de:10033/6211832019-08-30T11:33:29Zcom_10033_620613col_10033_620614
Andrade, Diego Fontana de
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Vukosavljevic, Branko
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Pohlmann, Adriana Raffin
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Guterres, Sílvia Stanisçuaski
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Windbergs, Maike
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Beck, Ruy Carlos Ruver
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Helmholtz-Institut für pharmazeitische Forschung Saarland, Universitäzscampus E8.1, 66123 Saarbrücken, Germany.
2017-11-22T15:15:25Z
2017-11-22T15:15:25Z
2017-11-20
Redispersible spray-dried lipid-core nanocapsules intended for oral delivery: the influence of the particle number on redispersibility. 2017:1-12 Pharm Dev Technol
1097-9867
29095657
10.1080/10837450.2017.1400559
http://hdl.handle.net/10033/621183
Pharmaceutical development and technology
This study proposes a new approach to produce easily redispersible spray-dried lipid-core nanocapsules (LNC) intended for oral administration, evaluating the influence of the particle number density of the fed sample. The proposed approach to develop redispersible spray-dried LNC formulations intended for oral route is innovative, evidencing the needing of an optimization of the initial particle number density in the liquid suspension of nanocapsules. A mixture of maltodextrin and L-leucine (90:10 w/w) was used as drying adjuvant. Dynamic light scattering, turbidimetry, determination of surface area and pore size distribution, electron microscopy and confocal Raman microscopy (CRM) were used to characterize the proposed system and to better understand the differences in the redispersion behavior. An easily aqueous redispersion of the spray-dried powder composed of maltodextrin and L-leucine (90:10 w/w) was obtained, depending on the particle number density. Their surface area decreased in the presence of LNC. CRM enabled the visualization of the spatial distribution of the different compounds in the powders affording to better understand the influence of the particle number density of the fed sample on their redispersion behavior. This study shows the need for optimizing initial particle number density in the liquid formulation to develop redispersible spray-dried LNC powders.
en
http://creativecommons.org/licenses/by-nc-sa/4.0/
Redispersible spray-dried lipid-core nanocapsules intended for oral delivery: the influence of the particle number on redispersibility.
Article
This study proposes a new approach to produce easily redispersible spray-dried lipid-core nanocapsules (LNC) intended for oral administration, evaluating the influence of the particle number density of the fed sample. The proposed approach to develop redispersible spray-dried LNC formulations intended for oral route is innovative, evidencing the needing of an optimization of the initial particle number density in the liquid suspension of nanocapsules. A mixture of maltodextrin and L-leucine (90:10 w/w) was used as drying adjuvant. Dynamic light scattering, turbidimetry, determination of surface area and pore size distribution, electron microscopy and confocal Raman microscopy (CRM) were used to characterize the proposed system and to better understand the differences in the redispersion behavior. An easily aqueous redispersion of the spray-dried powder composed of maltodextrin and L-leucine (90:10 w/w) was obtained, depending on the particle number density. Their surface area decreased in the presence of LNC. CRM enabled the visualization of the spatial distribution of the different compounds in the powders affording to better understand the influence of the particle number density of the fed sample on their redispersion behavior. This study shows the need for optimizing initial particle number density in the liquid formulation to develop redispersible spray-dried LNC powders.
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oai:repository.helmholtz-hzi.de:10033/6212722019-08-30T11:31:23Zcom_10033_620613col_10033_620614
Serr, Isabelle
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Fürst, Rainer W
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Ott, Verena B
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Scherm, Martin G
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Nikolaev, Alexei
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500
Gökmen, Füsun
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Kälin, Stefanie
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Zillmer, Stephanie
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Bunk, Melanie
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Weigmann, Benno
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Kunschke, Nicole
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Loretz, Brigitta
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Lehr, Claus Michael
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http://orcid.org/0000-0002-5864-8462
Kirchner, Benedikt
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Haase, Bettina
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Pfaffl, Michael
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Waisman, Ari
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Willis, Richard A
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Ziegler, Anette-G
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Daniel, Carolin
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Helmholtz-Institut für pharmazeutische Forschung Saarland, Universitätscampus E8.1, 66123 Saarbrücken, Germany.
2018-02-09T09:40:33Z
2018-02-09T09:40:33Z
2016
miRNA92a targets KLF2 and the phosphatase PTEN signaling to promote human T follicular helper precursors in T1D islet autoimmunity. 2016, 113 (43):E6659-E6668 Proc. Natl. Acad. Sci. U.S.A.
1091-6490
27791035
10.1073/pnas.1606646113
http://hdl.handle.net/10033/621272
Proceedings of the National Academy of Sciences of the United States of America
PMC5087025
Aberrant immune activation mediated by T effector cell populations is pivotal in the onset of autoimmunity in type 1 diabetes (T1D). T follicular helper (TFH) cells are essential in the induction of high-affinity antibodies, and their precursor memory compartment circulates in the blood. The role of TFH precursors in the onset of islet autoimmunity and signaling pathways regulating their differentiation is incompletely understood. Here, we provide direct evidence that during onset of islet autoimmunity, the insulin-specific target T-cell population is enriched with a C-X-C chemokine receptor type 5 (CXCR5)+CD4+ TFH precursor phenotype. During onset of islet autoimmunity, the frequency of TFH precursors was controlled by high expression of microRNA92a (miRNA92a). miRNA92a-mediated TFH precursor induction was regulated by phosphatase and tension homolog (PTEN) - phosphoinositol-3-kinase (PI3K) signaling involving PTEN and forkhead box protein O1 (Foxo1), supporting autoantibody generation and triggering the onset of islet autoimmunity. Moreover, we identify Krueppel-like factor 2 (KLF2) as a target of miRNA92a in regulating human TFH precursor induction. Importantly, a miRNA92a antagomir completely blocked induction of human TFH precursors in vitro. More importantly, in vivo application of a miRNA92a antagomir to nonobese diabetic (NOD) mice with ongoing islet autoimmunity resulted in a significant reduction of TFH precursors in peripheral blood and pancreatic lymph nodes. Moreover, miRNA92a antagomir application reduced immune infiltration and activation in pancreata of NOD mice as well as humanized NOD Scid IL2 receptor gamma chain knockout (NSG) human leucocyte antigen (HLA)-DQ8 transgenic animals. We therefore propose that miRNA92a and the PTEN-PI3K-KLF2 signaling network could function as targets for innovative precision medicines to reduce T1D islet autoimmunity.
en
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5087025/
http://creativecommons.org/licenses/by-nc-sa/4.0/
Adolescent
Animals
Antagomirs
Autoantibodies
Autoimmunity
Child
Diabetes Mellitus, Type 1
Female
Forkhead Box Protein O1
Gene Expression Regulation
Humans
Islets of Langerhans
Kruppel-Like Transcription Factors
Male
Mice
Mice, Inbred NOD
Mice, Transgenic
MicroRNAs
PTEN Phosphohydrolase
Phosphatidylinositol 3-Kinases
Primary Cell Culture
Receptors, CXCR5
Signal Transduction
T-Lymphocytes, Helper-Inducer
miRNA92a targets KLF2 and the phosphatase PTEN signaling to promote human T follicular helper precursors in T1D islet autoimmunity.
Article
2018-06-12T23:17:00Z
Aberrant immune activation mediated by T effector cell populations is pivotal in the onset of autoimmunity in type 1 diabetes (T1D). T follicular helper (TFH) cells are essential in the induction of high-affinity antibodies, and their precursor memory compartment circulates in the blood. The role of TFH precursors in the onset of islet autoimmunity and signaling pathways regulating their differentiation is incompletely understood. Here, we provide direct evidence that during onset of islet autoimmunity, the insulin-specific target T-cell population is enriched with a C-X-C chemokine receptor type 5 (CXCR5)+CD4+ TFH precursor phenotype. During onset of islet autoimmunity, the frequency of TFH precursors was controlled by high expression of microRNA92a (miRNA92a). miRNA92a-mediated TFH precursor induction was regulated by phosphatase and tension homolog (PTEN) - phosphoinositol-3-kinase (PI3K) signaling involving PTEN and forkhead box protein O1 (Foxo1), supporting autoantibody generation and triggering the onset of islet autoimmunity. Moreover, we identify Krueppel-like factor 2 (KLF2) as a target of miRNA92a in regulating human TFH precursor induction. Importantly, a miRNA92a antagomir completely blocked induction of human TFH precursors in vitro. More importantly, in vivo application of a miRNA92a antagomir to nonobese diabetic (NOD) mice with ongoing islet autoimmunity resulted in a significant reduction of TFH precursors in peripheral blood and pancreatic lymph nodes. Moreover, miRNA92a antagomir application reduced immune infiltration and activation in pancreata of NOD mice as well as humanized NOD Scid IL2 receptor gamma chain knockout (NSG) human leucocyte antigen (HLA)-DQ8 transgenic animals. We therefore propose that miRNA92a and the PTEN-PI3K-KLF2 signaling network could function as targets for innovative precision medicines to reduce T1D islet autoimmunity.
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Helmholtz Zentrum für Infektionsforschung Repository
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oai:repository.helmholtz-hzi.de:10033/6212872019-08-30T11:33:30Zcom_10033_620613col_10033_620614
Graef, Florian
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Michel, Jean-Philippe
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Wirth, Marius
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De Rossi, Chiara
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Windbergs, Maike
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Rosilio, Véronique
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Ducho, Christian
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Gordon, Sarah
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Lehr, Claus Michael
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http://orcid.org/0000-0002-5864-8462
HIPS, Helmholtz-Institut für pharmazeutische Forschung Saarland, Universitätscampus E8.1, 66123 Saarbrücken, Germany.
2018-02-19T15:43:35Z
2018-02-19T15:43:35Z
2016
The bacterial cell envelope as delimiter of anti-infective bioavailability - An in vitro permeation model of the Gram-negative bacterial inner membrane. 2016, 243:214-224 J Control Release
1873-4995
27769806
10.1016/j.jconrel.2016.10.018
http://hdl.handle.net/10033/621287
Journal of controlled release : official journal of the Controlled Release Society
Gram-negative bacteria possess a unique and complex cell envelope, composed of an inner and outer membrane separated by an intermediate cell wall-containing periplasm. This tripartite structure acts intrinsically as a significant biological barrier, often limiting the permeation of anti-infectives, and so preventing such drugs from reaching their target. Furthermore, identification of the specific permeation-limiting envelope component proves difficult in the case of many anti-infectives, due to the challenges associated with isolation of individual cell envelope structures in bacterial culture. The development of an in vitro permeation model of the Gram-negative inner membrane, prepared by repeated coating of physiologically-relevant phospholipids on Transwell®filter inserts, is therefore reported, as a first step in the development of an overall cell envelope model. Characterization and permeability investigations of model compounds as well as anti-infectives confirmed the suitability of the model for quantitative and kinetically-resolved permeability assessment, and additionally confirmed the importance of employing bacteria-specific base materials for more accurate mimicking of the inner membrane lipid composition - both advantages compared to the majority of existing in vitro approaches. Additional incorporation of further elements of the Gram-negative bacterial cell envelope could ultimately facilitate model application as a screening tool in anti-infective drug discovery or formulation development.
en
http://creativecommons.org/licenses/by-nc-sa/4.0/
Anti-Bacterial Agents
Biological Availability
Cell Membrane
Cell Membrane Permeability
Gram-Negative Bacteria
Phospholipids
The bacterial cell envelope as delimiter of anti-infective bioavailability - An in vitro permeation model of the Gram-negative bacterial inner membrane.
Article
2018-06-13T00:43:02Z
Gram-negative bacteria possess a unique and complex cell envelope, composed of an inner and outer membrane separated by an intermediate cell wall-containing periplasm. This tripartite structure acts intrinsically as a significant biological barrier, often limiting the permeation of anti-infectives, and so preventing such drugs from reaching their target. Furthermore, identification of the specific permeation-limiting envelope component proves difficult in the case of many anti-infectives, due to the challenges associated with isolation of individual cell envelope structures in bacterial culture. The development of an in vitro permeation model of the Gram-negative inner membrane, prepared by repeated coating of physiologically-relevant phospholipids on Transwell®filter inserts, is therefore reported, as a first step in the development of an overall cell envelope model. Characterization and permeability investigations of model compounds as well as anti-infectives confirmed the suitability of the model for quantitative and kinetically-resolved permeability assessment, and additionally confirmed the importance of employing bacteria-specific base materials for more accurate mimicking of the inner membrane lipid composition - both advantages compared to the majority of existing in vitro approaches. Additional incorporation of further elements of the Gram-negative bacterial cell envelope could ultimately facilitate model application as a screening tool in anti-infective drug discovery or formulation development.
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Helmholtz Zentrum für Infektionsforschung Repository
hzi@openrepository.com
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oai:repository.helmholtz-hzi.de:10033/6213132019-08-30T11:33:30Zcom_10033_620613col_10033_620614
Castoldi, Arianna
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Herr, Christian
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Niederstraßer, Julia
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Labouta, Hagar Ibrahim
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Lehr, Claus Michael
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http://orcid.org/0000-0002-5864-8462
HIPS, Helmholtz-Institut für pharmazeutische Forschung Saarland, Universitätscampus 8.1, 66123 Saarbrücken, Germany.
2018-03-07T15:26:15Z
2018-03-07T15:26:15Z
2017-09
Calcifediol-loaded liposomes for local treatment of pulmonary bacterial infections. 2017, 118:62-67 Eur J Pharm Biopharm
1873-3441
27888144
10.1016/j.ejpb.2016.11.026
http://hdl.handle.net/10033/621313
European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V
The influence of vitamin D3 and its metabolites calcifediol (25(OH)D) and calcitriol on immune regulation and inflammation is well described, and raises the question of potential benefit against bacterial infections. In the current study, 25(OH)D was encapsulated in liposomes to enable aerosolisation, and tested for the ability to prevent pulmonary infection by Pseudomonas aeruginosa. Prepared 25(OH)D-loaded liposomes were nanosized and monodisperse, with a negative surface charge and a 25(OH)D entrapment efficiency of approximately 23%. Jet nebulisation of liposomes was seen to yield an aerosol suitable for tracheo-bronchial deposition. Interestingly, 25(OH)D in either liposomes or ethanolic solution had no effect on the release of the proinflammatory cytokine KC from Pseudomonas-infected murine epithelial cells (LA-4); treatment of infected, human bronchial 16-HBE cells with 25(OH)D liposomes however resulted in a significant reduction in bacterial survival. Together with the importance of selecting an application-appropriate in vitro model, the current study illustrates the feasibility and practicality of employing liposomes as a means to achieve 25(OH)D lung deposition. 25(OH)D-loaded liposomes further demonstrated promising effects regarding prevention of Pseudomonas infection in human bronchial epithelial cells.
en
http://creativecommons.org/licenses/by-nc-sa/4.0/
Calcifediol-loaded liposomes for local treatment of pulmonary bacterial infections.
Article
2018-06-13T05:42:49Z
The influence of vitamin D3 and its metabolites calcifediol (25(OH)D) and calcitriol on immune regulation and inflammation is well described, and raises the question of potential benefit against bacterial infections. In the current study, 25(OH)D was encapsulated in liposomes to enable aerosolisation, and tested for the ability to prevent pulmonary infection by Pseudomonas aeruginosa. Prepared 25(OH)D-loaded liposomes were nanosized and monodisperse, with a negative surface charge and a 25(OH)D entrapment efficiency of approximately 23%. Jet nebulisation of liposomes was seen to yield an aerosol suitable for tracheo-bronchial deposition. Interestingly, 25(OH)D in either liposomes or ethanolic solution had no effect on the release of the proinflammatory cytokine KC from Pseudomonas-infected murine epithelial cells (LA-4); treatment of infected, human bronchial 16-HBE cells with 25(OH)D liposomes however resulted in a significant reduction in bacterial survival. Together with the importance of selecting an application-appropriate in vitro model, the current study illustrates the feasibility and practicality of employing liposomes as a means to achieve 25(OH)D lung deposition. 25(OH)D-loaded liposomes further demonstrated promising effects regarding prevention of Pseudomonas infection in human bronchial epithelial cells.
ORIGINAL
Castoldi et al.pdf
Castoldi et al.pdf
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Helmholtz Zentrum für Infektionsforschung Repository
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oai:repository.helmholtz-hzi.de:10033/6213302019-08-30T11:30:58Zcom_10033_620613col_10033_620614
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http://orcid.org/0000-0002-5864-8462
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HIPS, Helmholtz-Institute für pharmazeutische Forschung Saarland, Universitätscampus E8.1, 66123 Saarbrücken, Germany.
2018-03-22T10:07:29Z
2018-03-22T10:07:29Z
2018-01-03
A miRNA181a/NFAT5 axis links impaired T cell tolerance induction with autoimmune type 1 diabetes. 2018, 10 (422) Sci Transl Med
1946-6242
29298866
10.1126/scitranslmed.aag1782
http://hdl.handle.net/10033/621330
Science translational medicine
Molecular checkpoints that trigger the onset of islet autoimmunity or progression to human type 1 diabetes (T1D) are incompletely understood. Using T cells from children at an early stage of islet autoimmunity without clinical T1D, we find that a microRNA181a (miRNA181a)-mediated increase in signal strength of stimulation and costimulation links nuclear factor of activated T cells 5 (NFAT5) with impaired tolerance induction and autoimmune activation. We show that enhancing miRNA181a activity increases NFAT5 expression while inhibiting FOXP3+regulatory T cell (Treg) induction in vitro. Accordingly, Treginduction is improved using T cells from NFAT5 knockout (NFAT5ko) animals, whereas altering miRNA181a activity does not affect Treginduction in NFAT5ko T cells. Moreover, high costimulatory signals result in phosphoinositide 3-kinase (PI3K)-mediated NFAT5, which interferes with FoxP3+Treginduction. Blocking miRNA181a or NFAT5 increases Treginduction in murine and humanized models and reduces murine islet autoimmunity in vivo. These findings suggest targeting miRNA181a and/or NFAT5 signaling for the development of innovative personalized medicines to limit islet autoimmunity.
en
http://creativecommons.org/licenses/by-nc-sa/4.0/
A miRNA181a/NFAT5 axis links impaired T cell tolerance induction with autoimmune type 1 diabetes.
Article
2018-06-12T17:22:37Z
Molecular checkpoints that trigger the onset of islet autoimmunity or progression to human type 1 diabetes (T1D) are incompletely understood. Using T cells from children at an early stage of islet autoimmunity without clinical T1D, we find that a microRNA181a (miRNA181a)-mediated increase in signal strength of stimulation and costimulation links nuclear factor of activated T cells 5 (NFAT5) with impaired tolerance induction and autoimmune activation. We show that enhancing miRNA181a activity increases NFAT5 expression while inhibiting FOXP3+regulatory T cell (Treg) induction in vitro. Accordingly, Treginduction is improved using T cells from NFAT5 knockout (NFAT5ko) animals, whereas altering miRNA181a activity does not affect Treginduction in NFAT5ko T cells. Moreover, high costimulatory signals result in phosphoinositide 3-kinase (PI3K)-mediated NFAT5, which interferes with FoxP3+Treginduction. Blocking miRNA181a or NFAT5 increases Treginduction in murine and humanized models and reduces murine islet autoimmunity in vivo. These findings suggest targeting miRNA181a and/or NFAT5 signaling for the development of innovative personalized medicines to limit islet autoimmunity.
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2019-08-30 11:30:58.693
Helmholtz Zentrum für Infektionsforschung Repository
hzi@openrepository.com
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oai:repository.helmholtz-hzi.de:10033/6213442019-08-30T11:35:33Zcom_10033_620613col_10033_620614
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http://orcid.org/0000-0002-5864-8462
HIPS, Helmholtz-Institut für pharmazeutische Forschung Saarland, Universitätscampus 8.1, 66123 Saarbrücken, Germany.
2018-04-11T12:40:28Z
2018-04-11T12:40:28Z
2018-03-01
Starch-Chitosan Polyplexes: A Versatile Carrier System for Anti-Infectives and Gene Delivery 2018, 10 (3):252 Polymers
2073-4360
10.3390/polym10030252
http://hdl.handle.net/10033/621344
Polymers
http://www.mdpi.com/2073-4360/10/3/252
http://creativecommons.org/licenses/by-nc-sa/4.0/
Starch-Chitosan Polyplexes: A Versatile Carrier System for Anti-Infectives and Gene Delivery
Article
2018-06-13T04:27:34Z
ORIGINAL
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Helmholtz Zentrum für Infektionsforschung Repository
hzi@openrepository.com
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oai:repository.helmholtz-hzi.de:10033/6213842019-08-30T11:32:36Zcom_10033_620613col_10033_620614
Metz, Julia
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Knoth, Katharina
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Groß, Henrik
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Lehr, Claus-Michael
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Stäbler, Carolin
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Bock, Udo
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Hittinger, Marius
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HIPS, Helmholtz-Institute für pharmazeutische Forschung Saarland, Universitätscampus E8.1, 66123 Saarbrücken, Germany.
2018-05-31T07:33:07Z
2018-05-31T07:33:07Z
2018-05-10
29747472
http://hdl.handle.net/10033/621384
Hay fever is notoriously triggered when nasal mucosa is exposed to allergenic pollen. One possibility to overcome this pollen exposure may be the application of an ointment with physical protective effects. In this context, we have investigated Bepanthen Eye and Nose Ointment and the ointment basis petrolatum as reference while using contemporary in vitro techniques. Pollen from false ragweed () was used as an allergy-causing model deposited as aerosol using the Vitrocell Powder Chamber (VPC) on Transwell inserts, while being coated with either Bepanthen Eye and Nose Ointment and petrolatum. No pollen penetration into ointments was observed upon confocal scanning laser microscopy during an incubation period of 2 h at 37 °C. The cellular response was further investigated by integrating the MucilAir™ cell system in the VPC and by applying pollen to Bepanthen Eye and Nose Ointment covered cell cultures. For comparison, MucilAir™ were stimulated by lipopolysaccharides (LPS). No increased cytokine release of IL-6, TNF-α, or IL-8 was found after 4 h of pollen exposure, which demonstrates the safety of such ointments. Since nasal ointments act as a physical barrier against pollen, such preparations might support the prevention and management of hay fever.
Attribution-NonCommercial-ShareAlike 3.0 United States
http://creativecommons.org/licenses/by-nc-sa/3.0/us/
Bepanthen® Eye and Nose Ointment
3bacaf1b-c284-4dfa-b05f-6c413a164b7a
aerosol deposition in vitro system
da260dd1-7bc7-4533-94f0-6f0f6306aa8c
allergy prevention
bac9b6f4-04e2-4343-9e22-34b5c613c3b0
nasal mucosa
b0b8b1c9-d7c6-4914-b870-a3d1fb724599
pollen
c7b16617-832b-4ab0-bbd0-1c7c7f9a1e17
Combining MucilAir™ and Vitrocell Powder Chamber for the In Vitro Evaluation of Nasal Ointments in the Context of Aerosolized Pollen.
Article
2018-05-31T07:33:08Z
ORIGINAL
Metz et al.pdf
Metz et al.pdf
Open Access publication
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2019-08-30 11:32:36.614
Helmholtz Zentrum für Infektionsforschung Repository
hzi@openrepository.com
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oai:repository.helmholtz-hzi.de:10033/6214472019-08-30T11:26:10Zcom_10033_620613col_10033_620614
Ernst, Matthias
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John, Thomas
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Guenther, Marco
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Wagner, Christian
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500
Schaefer, Ulrich F
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500
Lehr, Claus-Michael
e25b30ba80302580419199334c0f4c6b
500
HIPS, Helmholtz-Institut für pharmazeutische Forschung Saarland, Universitätscampus 8.1, 66123 Saarbrücken, Germany.
2018-08-14T13:05:31Z
2018-08-14T13:05:31Z
2017-01-10
1542-0086
28076809
10.1016/j.bpj.2016.11.900
http://hdl.handle.net/10033/621447
In this study we have applied a model to explain the reported subdiffusion of particles in mucus, based on the measured mean squared displacements (MSD). The model considers Brownian diffusion of particles in a confined geometry, made from permeable membranes. The applied model predicts a normal diffusive behavior at very short and long time lags, as observed in several experiments. In between these timescales, we find that the "subdiffusive" regime is only a transient effect, MSD∝τ
en
Attribution-NonCommercial-ShareAlike 3.0 United States
http://creativecommons.org/licenses/by-nc-sa/3.0/us/
A Model for the Transient Subdiffusive Behavior of Particles in Mucus.
Article
Biophysical journal
2018-08-14T13:05:32Z
ORIGINAL
Ernst et al.pdf
Ernst et al.pdf
Open Access publication
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oai:hzi.openrepository.com:10033/621447
2019-08-30 11:26:10.039
Helmholtz Zentrum für Infektionsforschung Repository
hzi@openrepository.com
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oai:repository.helmholtz-hzi.de:10033/6214622019-08-30T11:29:14Zcom_10033_620613col_10033_620614
Pontes, Montcharles S.
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500
Montefusco-Pereira, Carlos V.
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500
Misra, Biswapriya B.
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Ribeiro-Junior, Howard L.
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Graciano, Daniela E.
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Santos, Jaqueline S.
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Nobrega, Michele A.S.
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Fernandes, Shaline S.L.
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Caires, Anderson R.L.
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Santiago, Etenaldo F.
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500
HIPS, Helmholtz-Institut für pharmazeutische Forschung Saarland, Universitätscampus 8.1, 66123 Saarbrücken, Germany.
2018-09-03T08:20:19Z
2018-09-03T08:20:19Z
22143173
10.1016/j.inpa.2018.07.001
http://hdl.handle.net/10033/621462
https://linkinghub.elsevier.com/retrieve/pii/S221431731830043X
Attribution-NonCommercial-ShareAlike 3.0 United States
http://creativecommons.org/licenses/by-nc-sa/3.0/us/
High-throughput phenotyping by applying digital morphometrics and fluorescence induction curves in seeds to identifying variations: A case study of Annona (Annonaceae) species
Article
Information Processing in Agriculture
2018-09-03T08:20:20Z
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Pontes et al.pdf
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Open Access publication
application/pdf
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10033/621462
oai:hzi.openrepository.com:10033/621462
2019-08-30 11:29:14.029
Helmholtz Zentrum für Infektionsforschung Repository
hzi@openrepository.com
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oai:repository.helmholtz-hzi.de:10033/6214822019-11-20T02:02:10Zcom_10033_620613com_10033_620656col_10033_620614col_10033_620685col_10033_620657
Frank, Julia
37b05dec655f22922f40f87cfa1017ef
500
Richter, Maximilian
24141d29e949e37ecadca1deccca9b1b
500
de Rossi, Chiara
e4bbb7143cb9c1919c21166809bf508f
500
Lehr, Claus-Michael
e25b30ba80302580419199334c0f4c6b
500
Fuhrmann, Kathrin
5cc1fdabba3e27db20d6c12dc949ec90
500
Fuhrmann, Gregor
45498f31c606876157afff3f8f6fbb9d
600
http://orcid.org/0000-0002-6688-5126
HIPS, Helmholtz-Institut für pharmazeutische Forschung Saarland, Universitätscampus 8.1, 66123 Saarbrücken, Germany.
2018-09-17T07:54:12Z
2018-09-17T07:54:12Z
2018-08-17
2045-2322
30120298
10.1038/s41598-018-30786-y
http://hdl.handle.net/10033/621482
Extracellular vesicles (EVs) are natural nanoparticles that play important roles in intercellular communication and are increasingly studied for biosignalling, pathogenesis and therapy. Nevertheless, little is known about optimal conditions for their transfer and storage, and the potential impact on preserving EV-loaded cargoes. We present the first comprehensive stability assessment of different widely available types of EVs during various storage conditions including -80 °C, 4 °C, room temperature, and freeze-drying (lyophilisation). Lyophilisation of EVs would allow easy handling at room temperature and thus significantly enhance their expanded investigation. A model enzyme, β-glucuronidase, was loaded into different types of EVs derived from mesenchymal stem cells, endothelial cells and cancer cells. Using asymmetric flow field-flow fractionation we proved that the model enzyme is indeed stably encapsulated into EVs. When assessing enzyme activity as indicator for EV stability, and in comparison to liposomes, we show that EVs are intrinsically stable during lyophilisation, an effect further enhanced by cryoprotectants. Our findings provide new insight for exploring lyophilisation as a novel storage modality and we create an important basis for standardised and advanced EV applications in biomedical research.
Attribution-NonCommercial-ShareAlike 3.0 United States
http://creativecommons.org/licenses/by-nc-sa/3.0/us/
Extracellular vesicles protect glucuronidase model enzymes during freeze-drying.
Article
Scientific reports
2018-09-17T07:54:13Z
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Frank et al.pdf.txt
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LICENSE
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MD5
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Frank_supp.pdf
Frank_supp.pdf
supplementary material
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10033/621482
oai:repository.helmholtz-hzi.de:10033/621482
2019-11-20 02:02:10.832
Helmholtz Zentrum für Infektionsforschung Repository
hzi@openrepository.com
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oai:repository.helmholtz-hzi.de:10033/6215082019-08-30T11:29:45Zcom_10033_620613col_10033_620614
Yasar, Hanzey
7074aa7a64909fbc424c1382b11086f9
500
Biehl, Alexander
5580b532b8eb7a4a49925283e00ffc14
500
De Rossi, Chiara
f2749c9e45c875fd008eac3a166f63c5
500
Koch, Marcus
fcb9284332d7940eb0530644049f3823
500
Murgia, Xabi
1004f0296c2f4e4d8341bf239ae5019c
500
Loretz, Brigitta
caab396a6e6faae9ada274b1a6c40fd5
500
Lehr, Claus-Michael
e25b30ba80302580419199334c0f4c6b
500
HIPS, Helmholtz-Institut für pharmazeutische Forschung Saarland, Universitätscampus 8.1, 66123 Saarbrücken, Germany.
2018-10-08T09:54:33Z
2018-10-08T09:54:33Z
2018-09-19
1477-3155
30231888
10.1186/s12951-018-0401-y
http://hdl.handle.net/10033/621508
Messenger RNA (mRNA) has gained remarkable attention as an alternative to DNA-based therapies in biomedical research. A variety of biodegradable nanoparticles (NPs) has been developed including lipid-based and polymer-based systems for mRNA delivery. However, both systems still lack in achieving an efficient transfection rate and a detailed understanding of the mRNA transgene expression kinetics. Therefore, quantitative analysis of the time-dependent translation behavior would provide a better understanding of mRNA's transient nature and further aid the enhancement of appropriate carriers with the perspective to generate future precision nanomedicines with quick response to treat various diseases. A lipid-polymer hybrid system complexed with mRNA was evaluated regarding its efficiency to transfect dendritic cells (DCs) by simultaneous live cell video imaging of both particle uptake and reporter gene expression. We prepared and optimized NPs consisting of poly (lactid-co-glycolid) (PLGA) coated with the cationic lipid 1, 2-di-O-octadecenyl-3-trimethylammonium propane abbreviated as LPNs. An earlier developed polymer-based delivery system (chitosan-PLGA NPs) served for comparison. Both NPs types were complexed with mRNA-mCherry at various ratios. While cellular uptake and toxicity of either NPs was comparable, LPNs showed a significantly higher transfection efficiency of ~ 80% while chitosan-PLGA NPs revealed only ~ 5%. Further kinetic analysis elicited a start of protein translation after 1 h, with a maximum after 4 h and drop of transgene expression after 48 h post-transfection, in agreement with the transient nature of mRNA. Charge-mediated complexation of mRNA to NPs enables efficient and fast cellular delivery and subsequent protein translation. While cellular uptake of both NP types was comparable, mRNA transgene expression was superior to polymer-based NPs when delivered by lipid-polymer NPs.
Attribution-NonCommercial-ShareAlike 3.0 United States
http://creativecommons.org/licenses/by-nc-sa/3.0/us/
Cationic lipid
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99743417-5e17-41b8-a1ef-c48734e2a90f
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mRNA
ec4bce1b-82c8-4230-bb6a-4ba1166a0009
Kinetics of mRNA delivery and protein translation in dendritic cells using lipid-coated PLGA nanoparticles.
Article
Journal of nanobiotechnology
2018-10-08T09:54:33Z
THUMBNAIL
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Generated Thumbnail
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Additional figures S1 to S6.pdf.jpg
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Yasar et al.pdf.txt
Yasar et al.pdf.txt
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LICENSE
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Yasar et al.pdf
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OPen Access publication
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10033/621508
oai:hzi.openrepository.com:10033/621508
2019-08-30 11:29:45.597
Helmholtz Zentrum für Infektionsforschung Repository
hzi@openrepository.com
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oai:repository.helmholtz-hzi.de:10033/6215122018-10-12T12:37:47Zcom_10033_620613col_10033_620614
Metz, Julia
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Knoth, Katharina
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Groß, Henrik
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Lehr, Claus-Michael
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Stäbler, Carolin
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Bock, Udo
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Hittinger, Marius
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HIPS, Helmholtz-Institut für pharmazeutische Forschung Saarland, Universitätscampus 8.1, 66123 Saarbrücken, Germany.
2018-10-10T13:49:02Z
2018-10-10T13:49:02Z
2018-05-10
1999-4923
29747472
10.3390/pharmaceutics10020056
http://hdl.handle.net/10033/621512
Hay fever is notoriously triggered when nasal mucosa is exposed to allergenic pollen. One possibility to overcome this pollen exposure may be the application of an ointment with physical protective effects. In this context, we have investigated Bepanthen® Eye and Nose Ointment and the ointment basis petrolatum as reference while using contemporary in vitro techniques. Pollen from false ragweed (Iva xanthiifolia) was used as an allergy-causing model deposited as aerosol using the Vitrocell® Powder Chamber (VPC) on Transwell® inserts, while being coated with either Bepanthen® Eye and Nose Ointment and petrolatum. No pollen penetration into ointments was observed upon confocal scanning laser microscopy during an incubation period of 2 h at 37 °C. The cellular response was further investigated by integrating the MucilAir™ cell system in the VPC and by applying pollen to Bepanthen® Eye and Nose Ointment covered cell cultures. For comparison, MucilAir™ were stimulated by lipopolysaccharides (LPS). No increased cytokine release of IL-6, TNF-α, or IL-8 was found after 4 h of pollen exposure, which demonstrates the safety of such ointments. Since nasal ointments act as a physical barrier against pollen, such preparations might support the prevention and management of hay fever. View Full-Text
Keywords: allergy prevention; pollen; aerosol deposition in vitro system; nasal mucosa; Bepanthen® Eye and Nose Ointment
Attribution-NonCommercial-ShareAlike 3.0 United States
http://creativecommons.org/licenses/by-nc-sa/3.0/us/
Bepanthen® Eye and Nose Ointment
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aerosol deposition in vitro system
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allergy prevention
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nasal mucosa
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pollen
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Combining MucilAir™ and Vitrocell Powder Chamber for the In Vitro Evaluation of Nasal Ointments in the Context of Aerosolized Pollen.
Article
Pharmaceutics
2018-10-10T13:49:03Z
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2018-10-12 12:37:47.027
Helmholtz Zentrum für Infektionsforschung Repository
hzi@openrepository.com
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oai:repository.helmholtz-hzi.de:10033/6215142019-08-30T11:29:45Zcom_10033_620613col_10033_620614
Niederstrasser, Julia
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Herr, Christian
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Wolf, Lisa
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Lehr, Claus M
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Beisswenger, Christoph
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Bals, Robert
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HIPS, Helmholtz-Institut für pharmazeutische Forschung Saarland, Universitätscampus 8.1, 66123 Saarbrücken, Germany.
2018-10-11T12:59:12Z
2018-10-11T12:59:12Z
2016-11-01
1098-5522
27400722
10.1128/IAI.00282-16
http://hdl.handle.net/10033/621514
Vitamin D (VitD) has a role in the regulation of calcium and phosphate metabolism and in addition impacts the activity of the immune system. VitD deficiency might be linked to increased susceptibility to respiratory tract infection. The aim of the present study was to characterize the impact of VitD deficiency on the susceptibility to bacterial infection in murine models. C57BL/6N mice were fed a diet with or without VitD for 10 weeks. The VitD-deficient or -sufficient mice were infected with Pseudomonas aeruginosa or Streptococcus pneumoniae The colonization and inflammatory response in the lung were analyzed at defined time points. The serum 25-hydroxy-VitD concentration was significantly lower in mice on the VitD-deficient diet. In infection experiments with Pseudomonas aeruginosa or Streptococcus pneumoniae, no differences could be observed in the numbers of viable bacteria or in differential cell counts in the bronchoalveolar lavage fluids. Measurements of inflammatory cytokines (KC and interleukin-1β [IL-1β]) did not show significant differences between the groups. In conclusion, VitD-deficient animals did not show significantly increased susceptibility to infection or an altered course of infection. The immune systems of humans and mice likely respond differently to VitD. Murine models are likely not appropriate for drawing conclusions on the role of VitD in human pulmonary host defense.
Attribution-NonCommercial-ShareAlike 3.0 United States
http://creativecommons.org/licenses/by-nc-sa/3.0/us/
Vitamin D Deficiency Does Not Result in a Breach of Host Defense in Murine Models of Pneumonia.
Article
Infection and immunity
2018-10-11T12:59:13Z
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oai:hzi.openrepository.com:10033/621514
2019-08-30 11:29:45.923
Helmholtz Zentrum für Infektionsforschung Repository
hzi@openrepository.com
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oai:repository.helmholtz-hzi.de:10033/6215422019-08-30T11:30:26Zcom_10033_620613col_10033_620614
Stucki, Janick D
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Schneider-Daum, Nicole
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HIPS, Helmholtz-Institut füt Pharmazeutische Forschung Saarland, Universitätscampus E8.1 66123 Saarbrücken, Germany.
2018-11-07T14:41:13Z
2018-11-07T14:41:13Z
2018-09-25
2045-2322
30254327
10.1038/s41598-018-32523-x
http://hdl.handle.net/10033/621542
Organs-on-chips have the potential to improve drug development efficiency and decrease the need for animal testing. For the successful integration of these devices in research and industry, they must reproduce in vivo contexts as closely as possible and be easy to use. Here, we describe a 'breathing' lung-on-chip array equipped with a passive medium exchange mechanism that provide an in vivo-like environment to primary human lung alveolar cells (hAEpCs) and primary lung endothelial cells. This configuration allows the preservation of the phenotype and the function of hAEpCs for several days, the conservation of the epithelial barrier functionality, while enabling simple sampling of the supernatant from the basal chamber. In addition, the chip design increases experimental throughput and enables trans-epithelial electrical resistance measurements using standard equipment. Biological validation revealed that human primary alveolar type I (ATI) and type II-like (ATII) epithelial cells could be successfully cultured on the chip over multiple days. Moreover, the effect of the physiological cyclic strain showed that the epithelial barrier permeability was significantly affected. Long-term co-culture of primary human lung epithelial and endothelial cells demonstrated the potential of the lung-on-chip array for reproducible cell culture under physiological conditions. Thus, this breathing lung-on-chip array, in combination with patients' primary ATI, ATII, and lung endothelial cells, has the potential to become a valuable tool for lung research, drug discovery and precision medicine.
Attribution-NonCommercial-ShareAlike 3.0 United States
http://creativecommons.org/licenses/by-nc-sa/3.0/us/
Medium throughput breathing human primary cell alveolus-on-chip model.
Article
Scientific reports
2018-11-07T14:41:14Z
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10033/621542
oai:hzi.openrepository.com:10033/621542
2019-08-30 11:30:26.536
Helmholtz Zentrum für Infektionsforschung Repository
hzi@openrepository.com
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oai:repository.helmholtz-hzi.de:10033/6215502019-08-30T11:31:43Zcom_10033_620613col_10033_620614
Ricci, Francesca
1a214f1588f774bf20a37f5e5019d866
500
Casiraghi, Costanza
2d894c04a75f62c7274b86af73657579
500
Storti, Matteo
2878912a500a558554e80708262f9f2a
500
D'Alò, Francesco
505302ce4192d5a9b74f30815f25a502
500
Catozzi, Chiara
7595192891a7310d5a662ef6a01858e8
500
Ciccimarra, Roberta
70e4a2f2371c50983a66a9330a4dbc06
500
Ravanetti, Francesca
e81b0dfceec21fc284a59c1cf3ea395f
500
Cacchioli, Antonio
8dcacb9ce66fdc0db4b32bc8456ba0cf
500
Villetti, Gino
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500
Civelli, Maurizio
eca9db1e4cc694c318ad3f46d431cd51
500
Murgia, Xabi
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500
Carnielli, Virgilio
0a1da82e6eb824872ced578d6f95fc70
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Salomone, Fabrizio
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500
HIPS, Helmholtz-Institut füt Pharmazeutische Forschung Saarland, Universitätscampus E8.1 66123 Saarbrücken, Germany.
2018-11-09T13:51:01Z
2018-11-09T13:51:01Z
2018-01-01
1932-6203
30001410
10.1371/journal.pone.0200542
http://hdl.handle.net/10033/621550
Nasal intermittent positive pressure ventilation (NIPPV) holds great potential as a primary ventilation support method for Respiratory Distress Syndrome (RDS). The use of NIPPV may also be of great value combined with minimally invasive surfactant delivery. Our aim was to implement an in vivo model of RDS, which can be managed with different non-invasive ventilation (NIV) strategies, including non-synchronized NIPPV, synchronized NIPPV (SNIPPV), and nasal continuous positive airway pressure (NCPAP). Forty-two surfactant-depleted adult rabbits were allocated in six different groups: three groups of animals were treated with only NIV for three hours (NIPPV, SNIPPV, and NCPAP groups), while three other groups were treated with surfactant (SF) followed by NIV (NIPPV+SF, SNIPPV+SF, and NCPAP+SF groups). Arterial gas exchange, ventilation indices, and dynamic compliance were assessed. Post-mortem the lungs were sampled for histological evaluation. Surfactant depletion was successfully achieved by repeated broncho-alveolar lavages (BALs). After BALs, all animals developed a moderate respiratory distress, which could not be reverted by merely applying NIV. Conversely, surfactant administration followed by NIV induced a rapid improvement of arterial oxygenation in all surfactant-treated groups. Breath synchronization was associated with a significantly better response in terms of gas exchange and dynamic compliance compared to non-synchronized NIPPV, showing also the lowest injury scores after histological assessment. The proposed in vivo model of surfactant deficiency was successfully managed with NCPAP, NIPPV, or SNIPPV; this model resembles a moderate respiratory distress and it is suitable for the preclinical testing of less invasive surfactant administration techniques.
Attribution-NonCommercial-ShareAlike 3.0 United States
http://creativecommons.org/licenses/by-nc-sa/3.0/us/
Surfactant replacement therapy in combination with different non-invasive ventilation techniques in spontaneously-breathing, surfactant-depleted adult rabbits.
Article
PloS one
2018-11-09T13:51:02Z
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Ricci et al.pdf
Ricci et al.pdf
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oai:hzi.openrepository.com:10033/621550
2019-08-30 11:31:43.679
Helmholtz Zentrum für Infektionsforschung Repository
hzi@openrepository.com
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oai:repository.helmholtz-hzi.de:10033/6216072018-12-05T15:08:05Zcom_10033_620613col_10033_620614
Metz, Julia
67143852-a3e9-4457-a892-fefd64eaaeaa
500
Knoth, Katharina
659e6627-b576-4fd6-a5b8-d47daaaee345
500
Groß, Henrik
a5178f37-bf18-4799-b874-ea34d8f6b23f
500
Lehr, Claus-Michael
0000-0002-5864-8462
Stäbler, Carolin
463e8906-8b8d-4d18-9ed8-fb2d65bb8010
500
Bock, Udo
70769a1a-ee35-427a-bf7c-be05982475dd
500
Hittinger, Marius
cf58ee78-6c74-4d01-b65c-833c271a26e6
500
HIPS, Helmholtz-Institut für Pharmazeutische Forschung Saarland, Universitätscampus E8.1 66123 Saarbrücken, Germany.
2018-12-05T15:08:05Z
2018-12-05T15:08:05Z
2018-05-10
1999-4923
29747472
10.3390/pharmaceutics10020056
http://hdl.handle.net/10033/621607
Hay fever is notoriously triggered when nasal mucosa is exposed to allergenic pollen.
One possibility to overcome this pollen exposure may be the application of an ointment with physical
protective effects. In this context, we have investigated Bepanthen® Eye and Nose Ointment and the
ointment basis petrolatum as reference while using contemporary in vitro techniques. Pollen from
false ragweed (Iva xanthiifolia) was used as an allergy-causing model deposited as aerosol using the
Vitrocell® Powder Chamber (VPC) on Transwell® inserts, while being coated with either Bepanthen®
Eye and Nose Ointment and petrolatum. No pollen penetration into ointments was observed upon
confocal scanning laser microscopy during an incubation period of 2 h at 37 ◦C. The cellular response
was further investigated by integrating the MucilAir™ cell system in the VPC and by applying pollen
to Bepanthen® Eye and Nose Ointment covered cell cultures. For comparison, MucilAir™ were
stimulated by lipopolysaccharides (LPS). No increased cytokine release of IL-6, TNF-α, or IL-8 was
found after 4 h of pollen exposure, which demonstrates the safety of such ointments. Since nasal
ointments act as a physical barrier against pollen, such preparations might support the prevention
and management of hay fever
Attribution-NonCommercial-ShareAlike 4.0 International
http://creativecommons.org/licenses/by-nc-sa/4.0/
Bepanthen® Eye and Nose Ointment
3bacaf1b-c284-4dfa-b05f-6c413a164b7a
500
aerosol deposition in vitro system
da260dd1-7bc7-4533-94f0-6f0f6306aa8c
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allergy prevention
bac9b6f4-04e2-4343-9e22-34b5c613c3b0
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nasal mucosa
b0b8b1c9-d7c6-4914-b870-a3d1fb724599
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pollen
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Combining MucilAir™ and Vitrocell Powder Chamber for the In Vitro Evaluation of Nasal Ointments in the Context of Aerosolized Pollen.
Article
Pharmaceutics
2018-12-05T15:08:05Z
LICENSE
license.txt
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10033/621607
oai:hzi.openrepository.com:10033/621607
2018-12-05 15:08:05.685
Helmholtz Zentrum für Infektionsforschung Repository
hzi@openrepository.com
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oai:repository.helmholtz-hzi.de:10033/6216242019-08-30T11:33:01Zcom_10033_620613col_10033_620614
Haque, A K M Ashiqul
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Dewerth, Alexander
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Antony, Justin S
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Riethmüller, Joachim
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Schweizer, Georg R
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Weinmann, Petra
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Latifi, Ngadhnjim
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Yasar, Hanzey
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Pedemonte, Nicoletta
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Sondo, Elvira
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Weidensee, Brian
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Laval, Julie
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Schlegel, Patrick
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Lehr, Claus-Michael
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Handgretinger, Rupert
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Kormann, Michael S D
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HIPS, Helmholtz-Institut füt Pharmazeutische Forschung Saarland, Universitätscampus E8.1 66123 Saarbrücken, Germany.
2018-12-19T14:51:50Z
2018-12-19T14:51:50Z
2018-11-13
2045-2322
30425265
10.1038/s41598-018-34960-0
http://hdl.handle.net/10033/621624
Gene therapy has always been a promising therapeutic approach for Cystic Fibrosis (CF). However, numerous trials using DNA or viral vectors encoding the correct protein resulted in a general low efficacy. In the last years, chemically modified messenger RNA (cmRNA) has been proven to be a highly potent, pulmonary drug. Consequently, we first explored the expression, function and immunogenicity of human (h)CFTR encoded by cmRNA
Nature publishing group
Attribution-NonCommercial-ShareAlike 4.0 International
http://creativecommons.org/licenses/by-nc-sa/4.0/
Chemically modified hCFTR mRNAs recuperate lung function in a mouse model of cystic fibrosis.
Article
Scientific reports
2018-12-19T14:51:50Z
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Haque et al.pdf.txt
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Open Access publication
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2019-08-30 11:33:01.976
Helmholtz Zentrum für Infektionsforschung Repository
hzi@openrepository.com
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oai:repository.helmholtz-hzi.de:10033/6216632019-08-30T11:33:27Zcom_10033_620613com_10033_620656com_10033_620644com_10033_620618col_10033_620614col_10033_620657col_10033_620619col_10033_620646
Castoldi, Arianna
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Empting, Martin
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http://orcid.org/0000-0002-0503-5830
De Rossi, Chiara
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Mayr, Karsten
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Dersch, Petra
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http://orcid.org/0000-0001-8177-3280
Hartmann, Rolf
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Müller, Rolf
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http://orcid.org/0000-0002-1042-5665
Gordon, Sarah
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Lehr, Claus-Michael
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HIPS, Helmholtz-Institut für Pharmazeutische Forschung Saarland, Universitätscampus E8.1 66123 Saarbrücken, Germany.
2019-01-18T15:45:31Z
2019-01-18T15:45:31Z
2018-12-05
Pharm Res. 2018 Dec 5;36(1):22. doi: 10.1007/s11095-018-2521-3.
1573-904X
30519925
10.1007/s11095-018-2521-3
http://hdl.handle.net/10033/621663
Pharmaceutical research
The objective of this work was to evaluate the potential of polymeric spherical and aspherical invasive nanocarriers, loaded with antibiotic, to access and treat intracellular bacterial infections. Aspherical nanocarriers were prepared by stretching of spherical precursors, and both aspherical and spherical nanocarriers were surface-functionalized with the invasive protein InvA497. The relative uptake of nanocarriers into HEp-2 epithelial cells was then assessed. Nanocarriers were subsequently loaded with a preparation of the non-permeable antibiotic gentamicin, and tested for their ability to treat HEp-2 cells infected with the enteroinvasive bacterium Shigella flexneri. InvA497-functionalized nanocarriers of both spherical and aspherical shape showed a significantly improved rate and extent of uptake into HEp-2 cells in comparison to non-functionalized nanocarriers. Functionalized and antibiotic-loaded nanocarriers demonstrated a dose dependent killing of intracellular S. flexneri. A slight but significant enhancement of intracellular bacterial killing was also observed with aspherical as compared to spherical functionalized nanocarriers at the highest tested concentration. InvA497-functionalized, polymer-based nanocarriers were able to efficiently deliver a non-permeable antibiotic across host cell membranes to affect killing of intracellular bacteria. Functionalized nanocarriers with an aspherical shape showed an interesting future potential for intracellular infection therapy.
en
Springer
Attribution-NonCommercial-ShareAlike 4.0 International
http://creativecommons.org/licenses/by-nc-sa/4.0/
AOT-gentamicin
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aspherical nanoparticles
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bacteriomimetic nanocarriers
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intracellular infection
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invasin
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Aspherical and Spherical InvA497-Functionalized Nanocarriers for Intracellular Delivery of Anti-Infective Agents.
Article
Pharmaceutical research
2019-01-18T15:45:32Z
THUMBNAIL
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Castoldi et al.pdf.txt
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ORIGINAL
Castoldi et al.pdf
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Open Access article
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2019-08-30 11:33:27.918
Helmholtz Zentrum für Infektionsforschung Repository
hzi@openrepository.com
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oai:repository.helmholtz-hzi.de:10033/6217372019-08-30T11:29:41Zcom_10033_620613col_10033_620614
Nnamani, Petra
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500
Ugwu, Agatha
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500
Ibezim, Emmanuel
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Onoja, Simon
ded828312b669bb9f443e9ad1e8e02b7
500
Odo, Amelia
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500
Windbergs, Maike
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500
Rossi, Chiara
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500
Lehr, Claus-Michael
e25b30ba80302580419199334c0f4c6b
500
Attama, Anthony
8d5172b0fa0a92f6715c858070d28b0f
500
HIPS, Helmholtz-Institut für Pharmazeutische Forschung Saarland, Universitätscampus E8.1 66123 Saarbrücken, Germany.
2019-04-02T13:20:06Z
2019-04-02T13:20:06Z
2019-02-13
1464-5246
30758259
10.1080/02652048.2019.1582724
http://hdl.handle.net/10033/621737
Journal of Microencapsulation
CONTEXT:
In this study, controlled ciprofloxacin (CIPRO) nanostrustructured lipid carriers of Precirol® ATO 5/Transcutol® HP (batch A) and tallow fat/Transcutol® HP (batch B) was carreid out.
OBJECTIVE:
The aim was to improve solubility and bioavailability of CIPRO.
OBJECTIVE:
Study of controlled ciprofloxacin (CIPRO) nanostructured lipid carriers of Precirol® ATO 5/Transcutol® HP (batch A) and tallow fat/Transcutol® HP (batch B).
METHODS:
CIPRO concentrations C1-5 (0.0, 0.2, 0.5, 0.8, and 1.0% w/w) as AC1-5 and BC1-5 were prepared by hot homogenisation and characterised by zetasizer, differential scanning calorimetry, Fourier transform infra-red spectroscopy, in vitro drug release and growth inhibitory zone diameter (IZD) on agar-seeded Bacillus subtilis.
RESULTS:
AC5 achieved polydispersed particles of ∼605 nm, 92% encapsulation efficiency (EE) and -28 mV similar to BC5 (∼789 nm, 91% EE, and -31 mV). Crystallinity indices (AC5 and BC5) were low at 3 and 5%, respectively. CIPRO release in AC5 was ∼98% in SGF (pH 1.2) and BC5 similarly ∼98% in SIF (pH 6.8).
CONCLUSIONS:
AC5 had superior growth inhibition of B. subtilis at lower concentration (1.2 µg/mL) than BC5 and CIPRO controls; hence could serve as possible sustained delivery system of CIPRO.
en
Taylor & Francis
Attribution-NonCommercial-ShareAlike 4.0 International
http://creativecommons.org/licenses/by-nc-sa/4.0/
Inhibition zone diameter
db43e2a2-1017-42ad-b16c-7a25e973271d
antimicrobial activity
5bd16a02-b1b7-4236-a861-98ef10f68dc8
ciprofloxacin
11dccde9-283c-4a3d-8729-6cc7f80f8118
nanostructured lipid carriers
21499963-4410-483c-a5c6-3c8b0faf7119
Preparation, characterisation and in vitro antibacterial property of ciprofloxacin-loaded nanostructured lipid carrier for treatment of Bacillus subtilis infection.
Article
Journal of microencapsulation
THUMBNAIL
2020-03-04
Nnamani et al.pdf.jpg
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2020-03-04
Nnamani et al.pdf.txt
Nnamani et al.pdf.txt
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2019-08-30 11:29:41.229
Helmholtz Zentrum für Infektionsforschung Repository
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oai:repository.helmholtz-hzi.de:10033/6217642019-08-30T11:35:08Zcom_10033_620613col_10033_620614
Murgia, Xabier
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500
Loretz, Brigitta
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Hartwig, Olga
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500
Hittinger, Marius
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500
Lehr, Claus-Michael
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500
HIPS, Helmholtz-Institut für Pharmazeutische Forschung Saarland, Universitätscampus E8.1 66123 Saarbrücken, Germany.
2019-05-08T08:02:13Z
2019-05-08T08:02:13Z
2018-01-15
Adv Drug Deliv Rev. 2018 Jan 15;124:82-97. doi: 10.1016/j.addr.2017.10.009. Epub 2017 Oct 26.
1872-8294
29106910
10.1016/j.addr.2017.10.009
http://hdl.handle.net/10033/621764
Advanced Drug Delivery Reviews
A layer of mucus covers the surface of all wet epithelia throughout the human body. Mucus is a hydrogel mainly composed of water, mucins (glycoproteins), DNA, proteins, lipids, and cell debris. This complex composition yields a tenacious viscoelastic hydrogel that lubricates and protects the exposed epithelia from external threats and enzymatic degradation. The natural protective role of mucus is nowadays acknowledged as a major barrier to be overcome in non-invasive drug delivery. The heterogeneity of mucus components offers a wide range of potential chemical interaction sites for macromolecules, while the mesh-like architecture given to mucus by the intermolecular cross-linking of mucin molecules results in a dense network that physically, and in a size-dependent manner, hinders the diffusion of nanoparticles through mucus. Consequently, drug diffusion, epithelial absorption, drug bioavailability, and ultimately therapeutic outcomes of mucosal drug delivery can be attenuated
en
Elsevier
Attribution-NonCommercial-ShareAlike 4.0 International
http://creativecommons.org/licenses/by-nc-sa/4.0/
Hydrogel
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Mucins
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Mucoadhesion
2ced35a0-09ad-4094-88b0-c42ba3f32ab4
Mucopenetration
499b42d1-d403-4ef6-9d57-fed05868c7a5
Mucosal drug delivery
2118a352-3133-4f6e-aeac-b691a7027af6
Nanoparticles
217d010b-05d5-4bb2-8f6a-e5eb60486212
PEGylation
6e20dd3f-4ff2-4df2-a14a-cf9ac8e3bcb1
Rheology
65bad27a-25b7-468e-9488-2353f94cbe9b
The role of mucus on drug transport and its potential to affect therapeutic outcomes.
Article
Advanced drug delivery reviews
2019-05-08T08:02:14Z
THUMBNAIL
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Murgia et al.pdf.txt
Murgia et al.pdf.txt
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text/plain
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Murgia et al.pdf
Murgia et al.pdf
original manuscript
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10033/621764
oai:hzi.openrepository.com:10033/621764
2019-08-30 11:35:08.675
Helmholtz Zentrum für Infektionsforschung Repository
hzi@openrepository.com
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oai:repository.helmholtz-hzi.de:10033/6217732019-08-30T11:28:45Zcom_10033_620613col_10033_620614
Kletting, Stephanie
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500
Barthold, Sarah
1be7e86d818b47ba6444ecb465ac716e
500
Repnik, Urska
ddd83cb806b5f325353aa94aaa481a67
500
Griffiths, Gareth
612c27a0e8e5bc75d7cba363971b0a09
500
Loretz, Brigitta
caab396a6e6faae9ada274b1a6c40fd5
500
Schneider-Daum, Nicole
98160be03011dc8dd14cdc48fbd09cb5
500
de Souza Carvalho-Wodarz, Cristiane
0c73691c8085e46d5a20a310da8c386d
500
Lehr, Claus-Michael
e25b30ba80302580419199334c0f4c6b
500
HIPS, Helmholtz-Institut für Pharmazeutische Forschung Saarland, Universitätscampus E8.1 66123 Saarbrücken, Germany.
2019-05-14T10:33:37Z
2019-05-14T10:33:37Z
2018-01-01
ALTEX. 2018;35(2):211-222. doi: 10.14573/altex.1607191. Epub 2017 Nov 23.
1868-596X
29169185
10.14573/altex.1607191
http://hdl.handle.net/10033/621773
ALTEX
The air-blood barrier is mainly composed of alveolar epithelial cells and macrophages. Whereas the epithelium acts
as a diffusional barrier, macrophages represent an immunological barrier, in particular for larger molecules and
nanoparticles.
This paper describes a new co-culture of human cell lines representing both cell types. Acquiring, culturing and maintaining primary alveolar epithelial cells presents significant logistical and technical difficulties. The recently established
human alveolar epithelial lentivirus immortalized cell line, hAELVi, when grown on permeable filters, forms monolayers
with high functional and morphological resemblance to alveolar type I cells. To model alveolar macrophages, the
human cell line THP-1 was seeded on pre-formed hAELVi monolayers.
The co-culture was characterized regarding cellular morphology, viability and barrier function. Macrophages were
homogenously distributed on the epithelium and could be kept in co-culture for up to 7 days. Transmission electron
microscopy showed loose contact between THP-1 and hAELVi cells. When grown at air liquid interface, both cells
were covered with extracellular matrix-like structure, which was absent in THP-1 mono-culture. In co-culture with macrophages, hAELVi cells displayed similar, sometimes even higher, transepithelial electrical resistance than in mono-cultures.
When exposed to silver and starch nanoparticles, hAELVi mono-cultures were more tolerant to the particles than THP-1
mono-cultures. Viability in the co-culture was similar to that of hAELVi mono-cultures. Transport studies with sodium
fluorescein in the presence/absence of EDTA proved that the co-culture acts as functional diffusion barrier. These data
demonstrate that hAELVi-/THP-1 co-cultures represent a promising model for safety and permeability studies of inhaled
chemicals, drugs and nanoparticles.
en
Springer Nature
Attribution-NonCommercial-ShareAlike 4.0 International
http://creativecommons.org/licenses/by-nc-sa/4.0/
In vitro model
bbed11ad-c44c-456b-8aec-9e1732331a3d
air-blood barrier
58b35eca-ed4d-4fec-b35a-c52a12f62e4b
nanoparticles
cabe19fd-ed15-419b-a82f-b750abab2279
nanotoxicology
46603bc7-0a7a-4f47-9113-660be7d7a197
pulmonary drug delivery
8c8afd4f-6118-4e9b-9272-385a789343cd
Co-culture of human alveolar epithelial (hAELVi) and macrophage (THP-1) cell lines.
Article
ALTEX
2019-05-14T10:33:38Z
THUMBNAIL
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10033/621773
oai:hzi.openrepository.com:10033/621773
2019-08-30 11:28:45.589
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hzi@openrepository.com
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oai:repository.helmholtz-hzi.de:10033/6219022019-08-30T11:26:11Zcom_10033_620613col_10033_620614
Menina, Sara
a728177d24918eafdccb8b011c4c1b6c
500
Eisenbeis, Janina
56840a4ef1135103061826105a6f4e7a
500
Kamal, Mohamed Ashraf M
d0b9fe4cd06031ab9d3353b4303d8fc0
500
Koch, Marcus
fcb9284332d7940eb0530644049f3823
500
Bischoff, Markus
81e3abfc51f6852266decec23339b88b
500
Gordon, Sarah
fe8bd36286e8c4766486b67cc27df81b
500
Loretz, Brigitta
caab396a6e6faae9ada274b1a6c40fd5
500
Lehr, Claus-Michael
e25b30ba80302580419199334c0f4c6b
500
HIPS, Helmholtz-Institut für Pharmazeutische Forschung Saarland, Universitätscampus E8.1 66123 Saarbrücken, Germany.
2019-08-15T13:45:07Z
2019-08-15T13:45:07Z
2019-07-22
2192-2659
31328434
10.1002/adhm.201900564
http://hdl.handle.net/10033/621902
Advanced Healthcare Materials
Bacterial invasion into eukaryotic cells and the establishment of intracellular infection has proven to be an effective means of resisting antibiotic action, as anti-infective agents commonly exhibit a poor permeability across the host cell membrane. Encapsulation of anti-infectives into nanoscaled delivery systems, such as liposomes, is shown to result in an enhancement of intracellular delivery. The aim of the current work is, therefore, to formulate colistin, a poorly permeable anti-infective, into liposomes suitable for oral delivery, and to functionalize these carriers with a bacteria-derived invasive moiety to enhance their intracellular delivery. Different combinations of phospholipids and cholesterol are explored to optimize liposomal drug encapsulation and stability in biorelevant media. These liposomes are then surface-functionalized with extracellular adherence protein (Eap), derived from Staphylococcus aureus. Treatment of HEp-2 and Caco-2 cells infected with Salmonella enterica using colistin-containing, Eap-functionalized liposomes resulted in a significant reduction of intracellular bacteria, in comparison to treatment with nonfunctionalized liposomes as well as colistin alone. This indicates that such bio-invasive carriers are able to facilitate intracellular delivery of colistin, as necessary for intracellular anti-infective activity. The developed Eap-functionalized liposomes, therefore, present a promising strategy for improving the therapy of intracellular infections.
en
Wiley-VCH
Attribution-NonCommercial-ShareAlike 4.0 International
http://creativecommons.org/licenses/by-nc-sa/4.0/
Eap
Staphylococcus aureus
bacterial invasion
bacteriomimetic nanocarriers
extracellular adherence proteins
simulated intestinal fluids
Bioinspired Liposomes for Oral Delivery of Colistin to Combat Intracellular Infections by Salmonella enterica.
Article
Advanced healthcare materials
2019-08-15T13:45:08Z
THUMBNAIL
Menina et al.pdf.jpg
Menina et al.pdf.jpg
Generated Thumbnail
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Menina et al.pdf.txt
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OPen Access publication
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https://hzi.openrepository.com/bitstream/10033/621902/1/Menina%20et%20al.pdf
c460b83a0aaf8c51c53d4be7e0309ead
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10033/621902
oai:hzi.openrepository.com:10033/621902
2019-08-30 11:26:11.08
Helmholtz Zentrum für Infektionsforschung Repository
hzi@openrepository.com
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oai:repository.helmholtz-hzi.de:10033/6219362019-09-14T01:29:41Zcom_10033_620613col_10033_620614
Artzy-Schnirman, Arbel
09d438bd0a55fc9534c9764d7de77d8b
300
Hobi, Nina
7a23c54c27459ac819c2e5d7ad523a81
500
Schneider-Daum, Nicole
98160be03011dc8dd14cdc48fbd09cb5
500
Guenat, Olivier T
1d403aa9556731a4f5bef193093f197b
300
Lehr, Claus-Michael
e25b30ba80302580419199334c0f4c6b
Sznitman, Josué
edec2fea2922384be747b72c7c0ba874
300
HIPS, Helmholtz-Institut für Pharmazeutische Forschung Saarland, Universitätscampus E8.1 66123 Saarbrücken, Germany.
2019-09-13T12:49:46Z
2019-09-13T12:49:46Z
2019-09-06
Eur J Pharm Biopharm. 2019 Sep 6. pii: S0939-6411(19)30785-4. doi: 10.1016/j.ejpb.2019.09.006.
1873-3441
31499161
10.1016/j.ejpb.2019.09.006
http://hdl.handle.net/10033/621936
European Journal of Pharmaceutics and Biopharmaceutics
With rapid advances in micro-fabrication processes and the availability of biologically-relevant lung cells, the development of lung-on-chip platforms is offering novel avenues for more realistic inhalation assays in pharmaceutical research, and thereby an opportunity to depart from traditional in vitro lung assays. As advanced models capturing the cellular pulmonary make-up at an air-liquid interface (ALI), lung-on-chips emulate both morphological features and biological functionality of the airway barrier with the ability to integrate respiratory breathing motions and ensuing tissue strains. Such in vitro systems allow importantly to mimic more realistic physiological respiratory flow conditions, with the opportunity to integrate physically-relevant transport determinants of aerosol inhalation therapy, i.e. recapitulating the pathway from airborne flight to deposition on the airway lumen. In this short opinion, we discuss such points and describe how these attributes are paving new avenues for exploring improved drug carrier designs (e.g. shape, size, etc.) and targeting strategies (e.g. conductive vs. respiratory regions) amongst other. We argue that while technical challenges still lie along the way in rendering in vitro lung-on-chip platforms more widespread across the general pharmaceutical research community, significant momentum is steadily underway in accelerating the prospect of establishing these as in vitro "gold standards"
en
Elsevier
info:eu-repo/grantAgreement/EC/H2020/ 677772
embargoedAccess
Attribution-NonCommercial-ShareAlike 4.0 International
http://creativecommons.org/licenses/by-nc-sa/4.0/
aerosols
cellular airway barrier
inhalation assays
microfluidics
organ-on-chip
Advanced in vitro lung-on-chip platforms for inhalation assays: From prospect to pipeline.
Article
European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V
2019-09-06T00:00:00Z
THUMBNAIL
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ArtzySchnirman et al.pdf.txt
ArtzySchnirman et al.pdf.txt
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ArtzySchnirman et al.pdf
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original manuscriipt
application/pdf
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10033/621936
oai:hzi.openrepository.com:10033/621936
2019-09-14 01:29:41.029
Helmholtz Zentrum für Infektionsforschung Repository
hzi@openrepository.com
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oai:repository.helmholtz-hzi.de:10033/6219372019-09-14T01:29:40Zcom_10033_620613col_10033_620614
Ho, Duy-Khiet
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Nichols, Brittany L B
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Edgar, Kevin J
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Murgia, Xabier
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500
Loretz, Brigitta
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Lehr, Claus-Michael
e25b30ba80302580419199334c0f4c6b
HIPS, Helmholtz-Institut für Pharmazeutische Forschung Saarland, Universitätscampus E8.1 66123 Saarbrücken, Germany.
2019-09-13T13:59:50Z
2019-09-13T13:59:50Z
2019-09-04
Eur J Pharm Biopharm. 2019 Sep 4. pii: S0939-6411(19)30620-4. doi: 10.1016/j.ejpb.2019.09.002.
1873-3441
31493510
10.1016/j.ejpb.2019.09.002
http://hdl.handle.net/10033/621937
European Journal of Pharmaceutics and Biopharmaceutics
Inhalation therapy has been reported as the most effective treatment for respiratory bacterial infections due to the increasing relevance of drug bioavailability. Drug delivery systems (DDS) have the capacity to overcome pulmonary biological barriers limiting the bioavailability of inhaled anti-infectives. This is important to eradicate bacterial infections and to prevent the development of bacterial resistance. Despite substantial efforts in the field, the current state-of-the-art often fails to achieve those goals, and we still observe increasing bacterial resistance. We give a brief insight on benefits and challenges in pulmonary delivery of anti-infectives. In the context of drug delivery development for pulmonary infections, particularly focusing on Pseudomonas aeruginosa (PA) infections, this mini review will critically discuss the main requirements, as well as the recent strategies of drug delivery system synthesis and preparation. Finally, interaction of DDS with crucial pulmonary biological barriers will be of great importance for the success of future applications of the developed DDS.
en
Elsevier
Attribution-NonCommercial-ShareAlike 4.0 International
http://creativecommons.org/licenses/by-nc-sa/4.0/
Pseudomonas aeruginosa
anti-infectives
antibiotics
biofilm
biological barriers
drug delivery
mucus
nanomedicine
nanoparticles
pulmonary infections
quorum sensing inhibitor
Challenges and Strategies in Drug Delivery Systems for Treatment of Pulmonary Infections.
Article
European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V
THUMBNAIL
2020-09-04
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2020-09-04
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Ho et al.pdf
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10033/621937
oai:hzi.openrepository.com:10033/621937
2019-09-14 01:29:40.966
Helmholtz Zentrum für Infektionsforschung Repository
hzi@openrepository.com
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oai:repository.helmholtz-hzi.de:10033/6219422019-09-17T02:31:02Zcom_10033_620613com_10033_620601col_10033_620614col_10033_620602
Durán, Verónica
d9fbab6d29a0d20531798ac48c5a943c
500
Yasar, Hanzey
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500
Becker, Jennifer
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500
Thiyagarajan, Durairaj
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300
Loretz, Brigitta
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500
Kalinke, Ulrich
f56a9fe34ec70d9c4effc3c0f66904da
600
http://orcid.org/0000-0003-0503-9564
Lehr, Claus-Michael
e25b30ba80302580419199334c0f4c6b
HIPS, Helmholtz-Institut für Pharmazeutische Forschung Saarland, Universitätscampus E8.1 66123 Saarbrücken, Germany.
2019-09-16T13:48:36Z
2019-09-16T13:48:36Z
2019-07-31
Nanomedicine. 2019 Jul 31;21:102073. doi: 10.1016/j.nano.2019.102073.
1549-9642
31376570
10.1016/j.nano.2019.102073
http://hdl.handle.net/10033/621942
Nanomedicine: Nanotechnology, Biology, and Medicine
Biodegradable polymeric nanoparticles (NP) made from poly (lactid-co-glycolide) acid (PLGA) and chitosan (CS) hold promise as innovative formulations for targeted delivery. Since interactions of such NP with primary human immune cells have not been characterized, yet, here we assessed the effect of PLGA or CS-PLGA NP treatment on human peripheral blood mononuclear cells (PBMC), as well as on monocyte-derived DC (moDC). Amongst PBMC, antigen presenting cells (APC) showed higher uptake of both NP preparations than lymphocytes. Furthermore, moDC internalized CS-PLGA NP more efficiently than PLGA NP, presumably because of receptor-mediated endocytosis. Consequently, CS-PLGA NP were delivered mostly to endosomal compartments, whereas PLGA NP primarily ended up in lysosomes. Thus, CS-PLGA NP confer enhanced delivery to endosomal compartments of APC, offering new therapeutic options to either induce or modulate APC function and to inhibit pathogens that preferentially infect APC.
Elsevier
Attribution-NonCommercial-ShareAlike 4.0 International
http://creativecommons.org/licenses/by-nc-sa/4.0/
Chitosan-PLGA NP
Intracellular trafficking
Monocyte-derived DC
Nanoparticles
PBMC
PLGA NP
Preferential uptake of chitosan-coated PLGA nanoparticles by primary human antigen presenting cells.
Article
Nanomedicine : nanotechnology, biology, and medicine
2019-09-16T13:48:36Z
THUMBNAIL
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TEXT
Durán et al.pdf.txt
Durán et al.pdf.txt
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ORIGINAL
Durán et al.pdf
Durán et al.pdf
Open Access article
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10033/621942
oai:hzi.openrepository.com:10033/621942
2019-09-17 02:31:02.358
Helmholtz Zentrum für Infektionsforschung Repository
hzi@openrepository.com
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oai:repository.helmholtz-hzi.de:10033/6219442019-09-18T03:36:38Zcom_10033_620613com_10033_620601col_10033_620614col_10033_620602
Salomon, Johanna J.
2de3c411b58b19487b2c4e7f0f72ecec
Gausterer, Julia C.
ef5172f5abf5881959da5ecf9d4c00a5
Selo, Mohammed Ali
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500
Hosoya, Ken Ichi
3d63af2cd512bf6f4917164bf58b8a41
500
Huwer, Hanno
470a9f61c72c61ca2050cde3e216732a
500
Schneider-Daum, Nicole
98160be03011dc8dd14cdc48fbd09cb5
500
Lehr, Claus Michael
abf087ce82af25bb53d54259fb3a9817
Ehrhardt, Carsten
80cf54aec838055398a09e09b1f9cd0b
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HIPS, Helmholtz-Institut für Pharmazeutische Forschung Saarland, Universitätscampus E8.1 66123 Saarbrücken, Germany.
Salomon, J.
2019-09-17T09:10:21Z
2019-09-17T09:10:21Z
2019-08-01
Pharmaceutics. 2019 Aug 7;11(8). pii: pharmaceutics11080396. doi: 10.3390/pharmaceutics11080396.
31394757
10.3390/pharmaceutics11080396
https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85071193528&origin=inward
http://hdl.handle.net/10033/621944
Pharmaceutics
2-s2.0-85071193528
SCOPUS_ID:85071193528
The carnitine transporter OCTN2 is associated with asthma and other inflammatory diseases. The aims of this work were (i) to determine carnitine uptake into freshly isolated human alveolar type I (ATI)-like epithelial cells in primary culture, (ii) to compare the kinetics of carnitine uptake between respiratory epithelial in vitro cell models, and (iii) to establish whether any cell line was a suitable model for studies of carnitine transport at the air-blood barrier. Levels of time-dependent [3H]-acetyl-l-carnitine uptake were similar in ATI-like, NCl-H441, and Calu-3 epithelial cells, whereas uptake into A549 cells was ~5 times higher. Uptake inhibition was more pronounced by OCTN2 modulators, such as l-Carnitine and verapamil, in ATI-like primary epithelial cells compared to NCl-H441 and Calu-3 epithelial cells. Our findings suggest that OCTN2 is involved in the cellular uptake of acetyl-l-carnitine at the alveolar epithelium and that none of the tested cell lines are optimal surrogates for primary cells.
en
MPDI
Pharmaceutics
8
11
Attribution-NonCommercial-ShareAlike 4.0 International
http://creativecommons.org/licenses/by-nc-sa/4.0/
Acetyl-l-carnitine
Asthma
Epithelial transport
In vitro models
Lung epithelium
OCTN2
Organic cation transporter
OCTN2-mediated acetyl-l-carnitine transport in human pulmonary epithelial cells in vitro
Article
2019-09-17T09:10:21Z
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Artzy-Schnirman, A.
2019-10-23T09:22:10Z
2019-10-23T09:22:10Z
2019-09-01
10.1002/adbi.201900026
https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85071983618&origin=inward
http://hdl.handle.net/10033/621990
Advanced Biosystems
2-s2.0-85071983618
SCOPUS_ID:85071983618
en
Wiley-VCH
info:eu-repo/grantAgreement/EC/H2020/677772
Advanced Biosystems
9
3
embargoedAccess
Attribution-NonCommercial-ShareAlike 4.0 International
http://creativecommons.org/licenses/by-nc-sa/4.0/
epithelial barrier
in vitro assays
microfluidics
organ-on-chip
pulmonary infection
Capturing the Onset of Bacterial Pulmonary Infection in Acini-On-Chips
Article
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oai:repository.helmholtz-hzi.de:10033/6220222019-11-21T02:06:58Zcom_10033_620613col_10033_620614
Formicola, Beatrice
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Dal Magro, Roberta
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Montefusco-Pereira, Carlos V
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Lehr, Claus-Michael
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Koch, Marcus
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HIPS, Helmholtz-Institut für Pharmazeutische Forschung Saarland, Universitätscampus E8.1 66123 Saarbrücken, Germany.
2019-11-20T15:36:02Z
2019-11-20T15:36:02Z
2019-11-11
J Nanobiotechnology. 2019 Nov 11;17(1):115. doi: 10.1186/s12951-019-0546-3.
1477-3155
31711496
10.1186/s12951-019-0546-3
http://hdl.handle.net/10033/622022
Journal of nanobiotechnology
We designed liposomes dually functionalized with ApoE-derived peptide (mApoE) and chlorotoxin (ClTx) to improve their blood-brain barrier (BBB) crossing. Our results demonstrated the synergistic activity of ClTx-mApoE in boosting doxorubicin-loaded liposomes across the BBB, keeping the anti-tumour activity of the drug loaded: mApoE acts promoting cellular uptake, while ClTx promotes exocytosis of liposomes.
en
BMC
Attribution-NonCommercial-ShareAlike 4.0 International
http://creativecommons.org/licenses/by-nc-sa/4.0/
Blood–brain barrier
Brain
Chlorotoxin
Doxorubicin
Drug delivery
Glioblastoma
Liposomes
Nanoparticles
The synergistic effect of chlorotoxin-mApoE in boosting drug-loaded liposomes across the BBB.
Article
Journal of nanobiotechnology
2019-11-20T15:36:02Z
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Helmholtz Zentrum für Infektionsforschung Repository
hzi@openrepository.com
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oai:repository.helmholtz-hzi.de:10033/6220592020-01-04T02:02:30Zcom_10033_620613com_10033_620618col_10033_620614col_10033_620619
Anversa Dimer, Frantiescoli
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de Souza Carvalho-Wodarz, Cristiane
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Goes, Adriely
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Cirnski, Katarina
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Herrmann, Jennifer
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Schmitt, Viktoria
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Pätzold, Linda
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Abed, Nadia
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de Rossi, Chiara
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Bischoff, Markus
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Couvreur, Patrick
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Müller, Rolf
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Lehr, Claus-Michael
e25b30ba80302580419199334c0f4c6b
HIPS, Helmholtz-Institut für Pharmazeutische Forschung Saarland, Universitätscampus E8.1 66123 Saarbrücken, Germany.
2020-01-03T13:32:06Z
2020-01-03T13:32:06Z
2019-11-18
Nanomedicine. 2019 Nov 18;24:102125. doi: 10.1016/j.nano.2019.102125.
1549-9642
31751769
10.1016/j.nano.2019.102125
http://hdl.handle.net/10033/622059
Nanomedicine: Nanotechnology, Biology, and Medicine
Drug delivery systems are promising for targeting antibiotics directly to infected tissues. To reach intracellular Staphylococcus aureus and Mycobacterium abscessus, we encapsulated clarithromycin in PLGA nanocapsules, suitable for aerosol delivery by nebulization of an aqueous dispersion. Compared to the same dose of free clarithromycin, nanoencapsulation reduced 1000 times the number of intracellular S. aureus in vitro. In RAW cells, while untreated S. aureus was located in acidic compartments, the treated ones were mostly situated in non-acidic compartments. Clarithromycin-nanocapsules were also effective against M. abscessus (70-80% killing efficacy). The activity of clarithromycin-nanocapsules against S. aureus was also confirmed in vivo, using a murine wound model as well as in zebrafish. The permeability of clarithromycin-nanocapsules across Calu-3 monolayers increased in comparison to the free drug, suggesting an improved delivery to sub-epithelial tissues. Thus, clarithromycin-nanocapsules are a promising strategy to target intracellular S. aureus and M. abscessus.
en
Elsevier
Attribution-NonCommercial-ShareAlike 4.0 International
http://creativecommons.org/licenses/by-nc-sa/4.0/
Clarithromycin
Mycobacterium abscessus
Nanoparticle
Permeability
Staphylococcus aureus
PLGA nanocapsules improve the delivery of clarithromycin to kill intracellular Staphylococcus aureus and Mycobacterium abscessus.
Article
Nanomedicine : nanotechnology, biology, and medicine
THUMBNAIL
2020-11-18
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2020-11-18
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TEXT
2020-11-18
Anversa Dimer et al.pdf.txt
Anversa Dimer et al.pdf.txt
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2020-11-18
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2020-11-18
Table S1.pdf.txt
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LICENSE
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Anversa Dimer et al.pdf
original manuscript
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Table S1.pdf
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supplementary table S1
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10033/622059
oai:repository.helmholtz-hzi.de:10033/622059
2020-01-04 02:02:30.272
Helmholtz Zentrum für Infektionsforschung Repository
hzi@openrepository.com
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oai:repository.helmholtz-hzi.de:10033/6221202020-02-06T02:10:02Zcom_10033_620613col_10033_620614
Sobot, Dunja
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Rouquette, Marie
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Buchy, Eric
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Pieters, Grégory
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Garcia-Argote, Sébastien
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Windbergs, Maike
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Desmaële, Didier
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2020-02-05T11:39:28Z
2020-02-05T11:39:28Z
2017-07-05
1525-0024
28606375
10.1016/j.ymthe.2017.05.016
http://hdl.handle.net/10033/622120
Selective delivery of anticancer drugs to rapidly growing cancercells can be achieved by taking advantage of their high receptor-mediated uptake of low-density lipoproteins (LDLs). Indeed, wehave recently discovered that nanoparticles made of the squa-lene derivative of the anticancer agent gemcitabine (SQGem)strongly interacted with the LDLs in the human blood. In thepresent study, we showed both in vitro and in vivo that suchinteraction led to the preferential accumulation of SQGem incancer cells (MDA-MB-231) with high LDL receptor expression.As a result, an improved pharmacological activity has beenobserved in MDA-MB-231 tumor-bearing mice, an experi-mental model with a low sensitivity to gemcitabine. Accord-ingly, we proved that the use of squalene moieties not onlyinduced the gemcitabine insertion into lipoproteins, but thatit could also be exploited to indirectly target cancer cells in vivo.
info:eu-repo/grantAgreement/EC/FP7/249835
openAccess
Attribution-NonCommercial-ShareAlike 4.0 International
http://creativecommons.org/licenses/by-nc-sa/4.0/
cancer
gemcitabine
indirect targeting
low-density lipoproteins
squalene-based nanoparticles
Circulating Lipoproteins: A Trojan Horse Guiding Squalenoylated Drugs to LDL-Accumulating Cancer Cells.
Article
Molecular therapy : the journal of the American Society of Gene Therapy
2020-02-05T11:39:28Z
THUMBNAIL
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TEXT
Sobot et al.pdf.txt
Sobot et al.pdf.txt
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LICENSE
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ORIGINAL
Sobot et al.pdf
Sobot et al.pdf
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10033/622120
oai:repository.helmholtz-hzi.de:10033/622120
2020-02-06 02:10:02.951
Helmholtz Zentrum für Infektionsforschung Repository
hzi@openrepository.com
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oai:repository.helmholtz-hzi.de:10033/6221472020-02-19T02:01:47Zcom_10033_620613col_10033_620614col_10033_620685
Montefusco-Pereira, Carlos V.
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Formicola, Beatrice
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500
Goes, Adriely
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500
Re, Francesca
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500
Marrano, Claudia A.
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500
Mantegazza, Francesco
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500
Carvalho-Wodarz, Cristiane
6d98db23d01f9e01fd7f26cf3a7318e1
Fuhrmann, Gregor
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http://orcid.org/0000-0002-6688-5126
Caneva, Enrico
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500
Nicotra, Francesco
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500
Lehr, Claus-Michael
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Russo, Laura
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HIPS, Helmholtz-Institut für Pharmazeutische Forschung Saarland, Universitätscampus E8.1 66123 Saarbrücken, Germany.
2020-02-18T14:00:05Z
2020-02-18T14:00:05Z
2020-04
Eur J Pharm Biopharm. 2020 Jan 30. pii: S0939-6411(20)30024-2. doi:10.1016/j.ejpb.2020.01.013.
0939-6411
32007589
10.1016/j.ejpb.2020.01.013
http://hdl.handle.net/10033/622147
European Journal of Pharmaceutics and Biopharmaceutics
By functionalizing the surface of PEG-liposomes with linkers bearing quaternary ammonium compounds (QACs), we generated novel bacteria disruptors with anti-adhesive properties and reduced cytotoxicity compared to free QACs. Furthermore, QAC-functionalized liposomes are a promising platform for future drug encapsulation. The QAC (11-mercaptoundecyl)-N,N,N-trimethylammonium bromide (MTAB) was attached to maleimide-functionalized liposomes (DSPE-PEG) via thiol linker. The MTAB-functionalized liposomes were physicochemically characterized and their biological activity, in terms of anti-adherence activity and biofilm prevention in Escherichia coli were assessed. The results showed that MTAB-functionalized liposomes inhibit bacterial adherence and biofilm formation while reducing MTAB toxicity.
Elsevier BV
Attribution-NonCommercial-ShareAlike 4.0 International
http://creativecommons.org/licenses/by-nc-sa/4.0/
Biotechnology
Pharmaceutical Science
General Medicine
Coupling quaternary ammonium surfactants to the surface of liposomes improves both antibacterial efficacy and host cell biocompatibility
Article
149
12-20
2020-02-18T14:00:07Z
THUMBNAIL
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Open Access article
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10033/622147
oai:repository.helmholtz-hzi.de:10033/622147
2020-02-19 02:01:47.413
Helmholtz Zentrum für Infektionsforschung Repository
hzi@openrepository.com
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oai:repository.helmholtz-hzi.de:10033/6221702020-03-12T03:28:25Zcom_10033_620613col_10033_620614
Metz, Julia K
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300
Scharnowske, Lara
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300
Hans, Fabian
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300
Schnur, Sabrina
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Knoth, Katharina
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Zimmer, Horst
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Limberger, Markus
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Groß, Henrik
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Lehr, Claus Michael
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Hittinger, Marius
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HIPS, Helmholtz-Institut für Pharmazeutische Forschung Saarland, Universitätscampus E8.1 66123 Saarbrücken, Germany.
2020-02-25T15:42:42Z
2020-02-25T15:42:42Z
2020-01-29
ALTEX. 2020 Jan 29. doi: 10.14573/altex.1910231.
1868-596X
32052853
10.14573/altex.1910231
http://hdl.handle.net/10033/622170
ALTEX
The development of new orally inhaled drug products requires the demonstration of safety which must be proven in animal experiments. New in vitro methods may replace, or at least reduce, these animal experiments provided they are able to correctly predict the safety or eventual toxicity in humans. However, the challenge is to link human in vitro data to human in vivo data. We here present a new approach to the safety assessment of excipients (SAFE) for pulmonary drug delivery. The SAFE model is based on a dose response curve of 23 excipients tested on the human pulmonary epithelial cell lines A549 and Calu-3. The resulting in vitro IC50 values were correlated with the FDA-approved concentration in pharmaceutical products for either pulmonary (if available) or parenteral administration. Setting a threshold of 0.1% (1 mg/mL) for either value yielded four safety classes, allowed to link IC50 data as measured on human cell cultures in vitro with the concentrations of the same compounds in FDA-approved drug products. The necessary in vitro data for novel excipients can be easily generated while the SAFE approach allows putting them in the context for eventual use in human pulmonary drug products. Excipients, that are most likely not safe for use in humans, can be early excluded from further pharmaceutical development. The SAFE approach helps thus to avoid unnecessary animal experiments.
en
Springer
Attribution-NonCommercial-ShareAlike 4.0 International
http://creativecommons.org/licenses/by-nc-sa/4.0/
3R principle
aerosol medicine
in vitro in vivo correlation
lungs
pulmonary drug development
Safety assessment of excipients (SAFE) for orally inhaled drug products.
Article
ALTEX
2020-02-25T15:42:42Z
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Metz et al.pdf
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Open Access publication
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10033/622170
oai:repository.helmholtz-hzi.de:10033/622170
2020-03-12 03:28:25.563
Helmholtz Zentrum für Infektionsforschung Repository
hzi@openrepository.com
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oai:repository.helmholtz-hzi.de:10033/6222322020-04-16T02:15:46Zcom_10033_620613col_10033_620614
Guo, Xiaojing
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Luo, Siwei
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Amidani, Davide
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Rivetti, Claudio
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HIPS, Helmholtz-Institut für Pharmazeutische Forschung Saarland, Universitätscampus E8.1 66123 Saarbrücken, Germany.
2020-04-15T15:06:55Z
2020-04-15T15:06:55Z
2020-03-13
PLoS One. 2020 Mar 13;15(3):e0230229. doi: 10.1371/journal.pone.0230229. eCollection 2020.
32168331
10.1371/journal.pone.0230229
http://hdl.handle.net/10033/622232
1932-6203
PloS one
Poractant alfa and Calsurf are two natural surfactants widely used in China for the treatment of neonatal respiratory distress syndrome, which are extracted from porcine and calf lungs, respectively. The purpose of this experimental study was to compare their in vitro characteristics and in vivo effects in the improvement of pulmonary function and protection of lung injury. The biophysical properties, ultrastructure, and lipid composition of both surfactant preparations were respectively analysed in vitro by means of Langmuir-Blodgett trough (LBT), atomic force microscopy (AFM), and liquid-chromatography mass-spectrometry (LC-MS). Then, as core pharmacological activity, both head-to-head (100 and 200 mg/kg for both surfactants) and licensed dose comparisons (70 mg/kg Calsurf vs. 200 mg/kg Poractant alfa) between the two surfactants were conducted as prophylaxis in preterm rabbits with primary surfactant deficiency, assessing survival time and rate and dynamic compliance of the respiratory system (Cdyn). Intrapulmonary surfactant pools, morphometric volume density as alveolar expansion (Vv), and lung injury scores were determined post mortem. AFM and LC-MS analysis revealed qualitative differences in the ultrastructure as well as in the lipid composition of both preparations. Calsurf showed a longer plateau region of the LBT isotherm and lower film compressibility. In vivo, both surfactant preparations improved Cdyn at any dose, although maximum benefits in terms of Vv and intrapulmonary surfactant pools were seen with the 200 mg/kg dose in both surfactants. The group of animals treated with 200 mg/kg of Poractant alfa showed a prolonged survival time and rate compared to untreated but ventilated controls, and significantly ameliorated lung injury compared to Calsurf at any dose, including 200 mg/kg. The overall outcomes suggest the pulmonary effects to be dose dependent for both preparations. The group of animals treated with 200 mg/kg of Poractant alfa showed a significant reduction of mortality. Compared to Calsurf, Poractant alfa exerted better effects if licensed doses were compared, which requires further investigation.
en
PLOS
Attribution-NonCommercial-ShareAlike 4.0 International
http://creativecommons.org/licenses/by-nc-sa/4.0/
In vitro characterization and in vivo comparison of the pulmonary outcomes of Poractant alfa and Calsurf in ventilated preterm rabbits.
Article
15
3
e0230229
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United States
2020-04-15T15:06:56Z
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Lehr, Claus-Michael
e25b30ba80302580419199334c0f4c6b
Sznitman, Josué
edec2fea2922384be747b72c7c0ba874
500
HIPS, Helmholtz-Institut für Pharmazeutische Forschung Saarland, Universitätscampus E8.1 66123 Saarbrücken, Germany.
2020-04-23T11:39:27Z
2020-04-23T11:39:27Z
2020-03-11
Expert Opin Drug Deliv. 2020 Mar 11:1-5. doi: 10.1080/17425247.2020.1738380.
32129105
10.1080/17425247.2020.1738380
http://hdl.handle.net/10033/622241
1744-7593
Expert opinion on drug delivery
[No abstracr available]
en
Taylor&Francis
Attribution-NonCommercial-ShareAlike 4.0 International
http://creativecommons.org/licenses/by-nc-sa/4.0/
Preclinical research
lung diseases
microfluidics
organ-on-chips
respiratory therapy
Advancing human pulmonary disease models in preclinical research: opportunities for .lung-on-chips.
Editorial
Other
1
5
Expert opinion on drug delivery
England
LICENSE
license.txt
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text/plain
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2020-04-23 11:39:27.845
Helmholtz Zentrum für Infektionsforschung Repository
hzi@openrepository.com
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Sznitman, Josué
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2020-04-23T13:04:17Z
2020-04-23T13:04:17Z
2020-03-11
Expert Opin Drug Deliv. 2020 Mar 11:1-5. doi: 10.1080/17425247.2020.1738380.
32129105
10.1080/17425247.2020.1738380
http://hdl.handle.net/10033/622242
1744-7593
Expert opinion on drug delivery
[No abstracr available]
en
Taylor&Francis
Attribution-NonCommercial-ShareAlike 4.0 International
http://creativecommons.org/licenses/by-nc-sa/4.0/
Preclinical research
lung diseases
microfluidics
organ-on-chips
respiratory therapy
Advancing human pulmonary disease models in preclinical research: opportunities for lung-on-chips..
Editorial
Other
1
5
Expert opinion on drug delivery
England
THUMBNAIL
2021-03-11
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2021-03-11
Artzy_Schnirman, Lehr and Sznitman.pdf.txt
Artzy_Schnirman, Lehr and Sznitman.pdf.txt
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Artzy_Schnirman, Lehr and Sznitman.pdf
Artzy_Schnirman, Lehr and Sznitman.pdf
ScholarOne Manuscript
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10033/622242
oai:repository.helmholtz-hzi.de:10033/622242
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Helmholtz Zentrum für Infektionsforschung Repository
hzi@openrepository.com
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Ho, Duy-Khiet
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Murgia, Xabier
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de Rossi, Chiara
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Christmann, Rebekka
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Hüfner de Mello Martins, Antonio G
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Koch, Marcus
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Andreas, Anastasia
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Herrmann, Jennifer
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Müller, Rolf
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Empting, Martin
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Hartmann, Rolf W
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Desmaele, Didier
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Loretz, Brigitta
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Couvreur, Patrick
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Lehr, Claus-Michael
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HIPS, Helmholtz-Institut für Pharmazeutische Forschung Saarland, Universitätscampus E8.1 66123 Saarbrücken, Germany.
2020-05-25T12:00:20Z
2020-05-25T12:00:20Z
2020-04-03
Angew Chem Int Ed Engl. 2020;10.1002/anie.202001407. doi:10.1002/anie.202001407.
32243047
10.1002/anie.202001407
http://hdl.handle.net/10033/622270
1521-3773
Angewandte Chemie (International ed. in English)
Elimination of pulmonary Pseudomonas aeruginosa (PA) infections is challenging to accomplish with antibiotic therapies, mainly due to resistance mechanisms. Quorum sensing inhibitors (QSIs) interfering with biofilm formation can thus complement antibiotics. For simultaneous and improved delivery of both active agents to the infection sites, self-assembling nanoparticles of a newly synthesized squalenyl hydrogen sulfate (SqNPs) were prepared. These nanocarriers allowed for remarkably high loading capacities of hydrophilic antibiotic tobramycin (Tob) and a novel lipophilic QSI at 30 % and circa 10 %, respectively. The drug-loaded SqNPs showed improved biofilm penetration and enhanced efficacy in relevant biological barriers (mucin/human tracheal mucus, biofilm), leading to complete eradication of PA biofilms at circa 16-fold lower Tob concentration than Tob alone. This study offers a viable therapy optimization and invigorates the research and development of QSIs for clinical use.
en
Wiley
Attribution-NonCommercial-ShareAlike 4.0 International
http://creativecommons.org/licenses/by-nc-sa/4.0/
Pseudomonas aeruginosa
biofilms
drug delivery
quorum sensing inhibitors
tobramycin
Squalenyl Hydrogen Sulfate Nanoparticles for Simultaneous Delivery of Tobramycin and an Alkylquinolone Quorum Sensing Inhibitor Enable the Eradication of P. aeruginosa Biofilm Infections.
Article
Angewandte Chemie (International ed. in English)
Germany
2020-05-25T12:00:21Z
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oai:repository.helmholtz-hzi.de:10033/622270
2020-05-26 01:28:59.058
Helmholtz Zentrum für Infektionsforschung Repository
hzi@openrepository.com
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