2024-03-29T10:42:01Zhttp://repository.helmholtz-hzi.de/oai/requestoai:repository.helmholtz-hzi.de:10033/1211022019-08-30T11:33:57Zcom_10033_620613col_10033_620614
Philippi, C
Loretz, B
Schaefer, U F
Lehr, C M
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
Telomerase as an emerging target to fight cancer--opportunities and challenges for nanomedicine.
article
oai:repository.helmholtz-hzi.de:10033/1461522019-08-30T11:33:57Zcom_10033_620613col_10033_620614
Schulze, Christine
Schaefer, Ulrich F
Ruge, Christian A
Wohlleben, Wendel
Lehr, Claus-Michael
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
Interaction of metal oxide nanoparticles with lung surfactant protein A.
Article
oai:repository.helmholtz-hzi.de:10033/1969722019-08-30T11:33:05Zcom_10033_620613col_10033_620614
Le Guével, Xavier
Daum, Nicole
Schneider, Marc
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
oai:repository.helmholtz-hzi.de:10033/2375932019-08-30T11:33:57Zcom_10033_620613col_10033_620614
Krejci, I
Piana, C
Howitz, S
Wegener, T
Fiedler, S
Zwanzig, M
Schmitt, D
Daum, N
Meier, K
Lehr, C M
Batista, U
Zemljic, S
Messerschmidt, J
Franzke, J
Wirth, M
Gabor, F
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
Process optimization and biocompatibility of cell carriers suitable for automated magnetic manipulation.
Article
oai:repository.helmholtz-hzi.de:10033/2471512019-08-30T11:34:47Zcom_10033_620613col_10033_620614
Hankin, Steve
Boraschi, Diana
Duschl, Albert
Lehr, Claus-Michael
Lichtenbeld, Hera
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
Archived with thanks to Nano Today
Towards nanotechnology regulation – Publish the unpublishable
Article
oai:repository.helmholtz-hzi.de:10033/2481112019-08-30T11:25:11Zcom_10033_620613col_10033_620614
May, Sabine
Jensen, Birte
Wolkenhauer, Markus
Schneider, Marc
Lehr, Claus Michael
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
oai:repository.helmholtz-hzi.de:10033/2659722019-08-30T11:28:24Zcom_10033_620613col_10033_620614
Jacobs, Simone
Bunt, Craig R
Wu, Zimei
Lehr, Claus-Michael
Rupenthal, Ilva D
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
oai:repository.helmholtz-hzi.de:10033/2665132019-08-30T11:34:22Zcom_10033_620613col_10033_620614
Dandekar, Prajakta
Jain, Ratnesh
Keil, Manuel
Loretz, Brigitta
Muijs, Leon
Schneider, Marc
Auerbach, Dagmar
Jung, Gregor
Lehr, Claus-Michael
Wenz, Gerhard
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
oai:repository.helmholtz-hzi.de:10033/2758922019-08-30T11:34:21Zcom_10033_620613col_10033_620614
Hansen, Steffi
Lehr, Claus-Michael
Schaefer, Ulrich F
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
oai:repository.helmholtz-hzi.de:10033/2759922019-08-30T11:25:43Zcom_10033_620613col_10033_620614
Hansen, Steffi
Lehr, Claus-Michael
Schaefer, Ulrich F
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
oai:repository.helmholtz-hzi.de:10033/2931602019-08-30T11:33:57Zcom_10033_620613col_10033_620614
Gómez-Mantilla, José-David
Casabó, Vicente Germán
Schaefer, Ulrich F
Lehr, Claus-Michael
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
oai:repository.helmholtz-hzi.de:10033/2944432019-08-30T11:33:30Zcom_10033_620613col_10033_620614
Franzen, Lutz
Vidlářová, Lucie
Kostka, Karl-Heinz
Schaefer, Ulrich F
Windbergs, Maike
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
oai:repository.helmholtz-hzi.de:10033/2959692019-08-30T11:33:29Zcom_10033_620613col_10033_620614
Kann, Birthe
Windbergs, Maike
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
oai:repository.helmholtz-hzi.de:10033/2971112019-08-30T11:34:22Zcom_10033_620613col_10033_620614
Franzen, Lutz
Selzer, Dominik
Fluhr, Joachim W
Schaefer, Ulrich F
Windbergs, Maike
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
oai:repository.helmholtz-hzi.de:10033/2972092019-08-30T11:34:22Zcom_10033_620613col_10033_620614
Schneider, Marc
Windbergs, Maike
Daum, Nicole
Loretz, Brigitta
Collnot, Eva-Maria
Hansen, Steffi
Schaefer, Ulrich F
Lehr, Claus-Michael
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
oai:repository.helmholtz-hzi.de:10033/2974452019-08-30T11:33:05Zcom_10033_620613col_10033_620614
Labouta, Hagar I
Thude, Sibylle
Schneider, Marc
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
Setup for investigating gold nanoparticle penetration through reconstructed skin and comparison to published human skin data.
Article
oai:repository.helmholtz-hzi.de:10033/3019992019-08-30T11:34:19Zcom_10033_620613col_10033_620614
Ali, Hussain
Collnot, Eva-Maria
Windbergs, Maike
Lehr, Claus-Michael
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
Archived with thanks to European Journal of Nanomedicine
Nanomedicines for the treatment of inflammatory bowel diseases
Article
oai:repository.helmholtz-hzi.de:10033/3057212019-08-30T11:27:46Zcom_10033_620613col_10033_620614
Mittal, Ankit
Raber, Anne S
Hansen, Steffi
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.
Archived with thanks to Human vaccines & immunotherapeutics
Particle based vaccine formulations for transcutaneous immunization.
Article
oai:repository.helmholtz-hzi.de:10033/3067012019-08-30T11:35:39Zcom_10033_620613col_10033_620614
Schrank, Simone
Kann, Birthe
Windbergs, Maike
Glasser, Benjamin J
Zimmer, Andreas
Khinast, Johannes
Roblegg, Eva
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
oai:repository.helmholtz-hzi.de:10033/3207932019-08-30T11:37:00Zcom_10033_620613col_10033_620614
Kirch, Julian
Schneider, Andreas
Abou, Bérengère
Hopf, Alexander
Schaefer, Ulrich F
Schneider, Marc
Schall, Christian
Wagner, Christian
Lehr, Claus-Michael
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
Optical tweezers reveal relationship between microstructure and nanoparticle penetration of pulmonary mucus.
Article
oai:repository.helmholtz-hzi.de:10033/3239072019-08-30T11:36:04Zcom_10033_620613col_10033_620614
Ucciferri, Nadia
Collnot, Eva-Marie
Gaiser, Birgit K
Tirella, Annalisa
Stone, Vicki
Domenici, Claudio
Lehr, Claus-Michael
Ahluwalia, Arti
2014-07-29T11:42:38Z
2014-07-29T11:42:38Z
2014-09
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
In vitro toxicological screening of nanoparticles on primary human endothelial cells and the role of flow in modulating cell response.
Article
oai:repository.helmholtz-hzi.de:10033/3328602019-08-30T11:32:41Zcom_10033_620613col_10033_620614
Nafee, Noha
Husari, Ayman
Maurer, Christine K
Lu, Cenbin
de Rossi, Chiara
Steinbach, Anke
Hartmann, Rolf W
Lehr, Claus-Michael
Schneider, Marc
2014-10-17T12:41:47Z
2014-10-17T12:41:47Z
2014-10-28
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
oai:repository.helmholtz-hzi.de:10033/3378492019-08-30T11:34:48Zcom_10033_620613col_10033_620614
Nnamani, Petra O
Hansen, Steffi
Windbergs, Maike
Lehr, Claus-Michael
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
oai:repository.helmholtz-hzi.de:10033/3386612019-08-30T11:36:33Zcom_10033_620613col_10033_620614
Goikoetxea, Estibalitz
Murgia, Xabier
Serna-Grande, Pablo
Valls-i-Soler, Adolf
Rey-Santano, Carmen
Rivas, Alejandro
Antón, Raúl
Basterretxea, Francisco J
Miñambres, Lorena
Méndez, Estíbaliz
Lopez-Arraiza, Alberto
Larrabe-Barrena, Juan Luis
Gomez-Solaetxe, Miguel Angel
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
oai:repository.helmholtz-hzi.de:10033/5563682019-08-30T11:31:18Zcom_10033_620613col_10033_620614
Jain, Ratnesh
Dandekar, Prajakta
Loretz, Brigitta
Koch, Marcus
Lehr, Claus-Michael
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.
Dimethylaminoethyl methacrylate copolymer-siRNA nanoparticles for silencing a therapeutically relevant gene in macrophages
Article
oai:repository.helmholtz-hzi.de:10033/5662642019-08-30T11:32:13Zcom_10033_620613col_10033_620614
Mahiny, Azita J
Dewerth, Alexander
Mays, Lauren E
Alkhaled, Mohammed
Mothes, Benedikt
Malaeksefat, Emad
Loretz, Brigitta
Rottenberger, Jennifer
Brosch, Darina M
Reautschnig, Philipp
Surapolchai, Pacharapan
Zeyer, Franziska
Schams, Andrea
Carevic, Melanie
Bakele, Martina
Griese, Matthias
Schwab, Matthias
Nürnberg, Bernd
Beer-Hammer, Sandra
Handgretinger, Rupert
Hartl, Dominik
Lehr, Claus-Michael
Kormann, Michael S D
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
oai:repository.helmholtz-hzi.de:10033/5765882019-08-30T11:28:24Zcom_10033_620613col_10033_620614
Nielsen, Line Hagner
Nagstrup, Johan
Gordon, Sarah
Keller, Stephan Sylvest
Østergaard, Jesper
Rades, Thomas
Müllertz, Anette
Boisen, Anja
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
oai:repository.helmholtz-hzi.de:10033/5770162019-08-30T11:36:32Zcom_10033_620613col_10033_620614
Rietscher, René
Thum, Carolin
Lehr, Claus-Michael
Schneider, Marc
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
oai:repository.helmholtz-hzi.de:10033/5786732019-08-30T11:36:32Zcom_10033_620613col_10033_620614
Schiller, Stefan
Hanefeld, Andrea
Schneider, Marc
Lehr, Claus-Michael
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
oai:repository.helmholtz-hzi.de:10033/5817982019-08-30T11:32:13Zcom_10033_620613col_10033_620614
Gordon, Sarah
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
Non-animal models of epithelial barriers (skin, intestine and lung) in research, industrial applications and regulatory toxicology
Meetings and Proceedings
oai:repository.helmholtz-hzi.de:10033/5828032019-08-30T11:33:57Zcom_10033_620613col_10033_620614
Salomon, Johanna J
Gausterer, Julia C
Yahara, Tohru
Hosoya, Ken-Ichi
Huwer, Hanno
Hittinger, Marius
Schneider-Daum, Nicole
Lehr, Claus-Michael
Ehrhardt, Carsten
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
oai:repository.helmholtz-hzi.de:10033/5828062019-08-30T11:34:21Zcom_10033_620613col_10033_620614
Schneider, Marc
Loretz, Brigitta
Windbergs, Maike
Schneider-Daum, Nicole
Schaefer, Ulrich F
Lehr, Claus-Michael
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
oai:repository.helmholtz-hzi.de:10033/5835112019-08-30T11:34:22Zcom_10033_620613col_10033_620614
Tscheka, Clemens
Hittinger, Marius
Lehr, Claus-Michael
Schneider-Daum, Nicole
Schneider, Marc
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
oai:repository.helmholtz-hzi.de:10033/5928202019-08-30T11:32:17Zcom_10033_620613col_10033_620614
Schwagerus, Elena
Sladek, Svenja
Buckley, Stephen T
Armas-Capote, Natalia
Alvarez de la Rosa, Diego
Harvey, Brian J
Fischer, Horst
Illek, Beate
Huwer, Hanno
Schneider-Daum, Nicole
Lehr, Claus-Michael
Ehrhardt, Carsten
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
oai:repository.helmholtz-hzi.de:10033/5936882019-08-30T11:28:51Zcom_10033_620613col_10033_620614
Dimer, Frantiescoli
de Souza Carvalho-Wodarz, Cristiane
Haupenthal, Jörg
Hartmann, Rolf
Lehr, Claus-Michael
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
oai:repository.helmholtz-hzi.de:10033/5958782019-08-30T11:34:17Zcom_10033_620613col_10033_620614
Sbrana, Tommaso
Ucciferri, Nadia
Favrè, Mèlanie
Ahmed, Sher
Collnot, Eva-Maria
Lehr, Claus-Michael
Ahluwalia, Arti
Liley, Martha
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
Dual flow bioreactor with ultrathin microporous TEER sensing membrane for evaluation of nanoparticle toxicity
Article
oai:repository.helmholtz-hzi.de:10033/5959592019-08-30T11:33:57Zcom_10033_620613col_10033_620614
Labouta, Hagar Ibrahim
Menina, Sara
Kochut, Annika
Gordon, Sarah
Geyer, Rebecca
Dersch, Petra
Lehr, Claus-Michael
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
oai:repository.helmholtz-hzi.de:10033/5959662019-08-30T11:30:58Zcom_10033_620613col_10033_620614
Guillot, Alexis
Couffin, Anne-Claude
Sejean, Xavier
Navarro, Fabrice
Limberger, Markus
Lehr, Claus-Michael
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
oai:repository.helmholtz-hzi.de:10033/5967202019-08-30T11:33:57Zcom_10033_620613col_10033_620614
Selzer, Dominik
Neumann, Dirk
Neumann, Heike
Kostka, Karl-Heinz
Lehr, Claus-Michael
Schaefer, Ulrich F
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
oai:repository.helmholtz-hzi.de:10033/5969672019-08-30T11:34:22Zcom_10033_620613col_10033_620614
Kenngott, Elisabeth E
Kiefer, Ruth
Schneider-Daum, Nicole
Hamann, Alf
Schneider, Marc
Schmitt, Manfred J
Breinig, Frank
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
oai:repository.helmholtz-hzi.de:10033/5992902019-08-30T11:33:57Zcom_10033_620613col_10033_620614
Mathes, C
Melero, A
Conrad, P
Vogt, T
Rigo, L
Selzer, D
Prado, W A
De Rossi, C
Garrigues, T M
Hansen, S
Guterres, S S
Pohlmann, A R
Beck, R C R
Lehr, C-M
Schaefer, U F
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
oai:repository.helmholtz-hzi.de:10033/6003022019-08-30T11:34:43Zcom_10033_620613col_10033_620614
Dandekar, P.
Jain, R.
Keil, M.
Loretz, B.
Koch, M.
Wenz, G.
Lehr, C.-M.
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
openAccess
Enhanced uptake and siRNA-mediated knockdown of a biologically relevant gene using cyclodextrin polyrotaxane
Article
oai:repository.helmholtz-hzi.de:10033/6047462019-08-30T11:26:12Zcom_10033_620613col_10033_620614
Kuehn, Anna
Kletting, Stephanie
de Souza Carvalho-Wodarz, Cristiane
Repnik, Urska
Griffiths, Gareth
Fischer, Ulrike
Meese, Eckart
Huwer, Hanno
Wirth, Dagmar
May, Tobias
Schneider-Daum, Nicole
Lehr, Claus Michael
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.
Human alveolar epithelial cells expressing tight junctions to model the air-blood barrier.
Article
oai:repository.helmholtz-hzi.de:10033/6091912019-08-30T11:25:11Zcom_10033_620613col_10033_620614
Nguyen, Duc Bach
Thuy Ly, Thi Bich
Wesseling, Mauro Carlos
Hittinger, Marius
Torge, Afra
Devitt, Andrew
Perrie, Yvonne
Bernhardt, Ingolf
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
oai:repository.helmholtz-hzi.de:10033/6113652019-08-30T11:33:57Zcom_10033_620613col_10033_620614
Rietscher, René
Czaplewska, Justyna A
Majdanski, Tobias C
Gottschaldt, Michael
Schubert, Ulrich S
Schneider, Marc
Lehr, Claus-Michael
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
oai:repository.helmholtz-hzi.de:10033/6149162019-08-30T11:34:22Zcom_10033_620613col_10033_620614
Bokkasam, Harish
Ernst, Matthias
Guenther, Marco
Wagner, Christian
Schaefer, Ulrich F
Lehr, Claus-Michael
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.
http://creativecommons.org/licenses/by-nc-sa/4.0/
Different macro- and micro-rheological properties of native porcine respiratory and intestinal mucus.
Article
oai:repository.helmholtz-hzi.de:10033/6173252019-08-30T11:33:29Zcom_10033_620613col_10033_620614
Gordon, Sarah
Daneshian, Mardas
Bouwstra, Joke
Caloni, Francesca
Constant, Samuel
Davies, Donna E
Dandekar, Gudrun
Guzman, Carlos A
Fabian, Eric
Haltner, Eleonore
Hartung, Thomas
Hasiwa, Nina
Hayden, Patrick
Kandarova, Helena
Khare, Sangeeta
Krug, Harald F
Kneuer, Carsten
Leist, Marcel
Lian, Guoping
Marx, Uwe
Metzger, Marco
Ott, Katharina
Prieto, Pilar
Roberts, Michael S
Roggen, Erwin L
Tralau, Tewes
van den Braak, Claudia
Walles, Heike
Lehr, Claus-Michael
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/
Non-animal models of epithelial barriers (skin, intestine and lung) in research, industrial applications and regulatory toxicology.
Article
oai:repository.helmholtz-hzi.de:10033/6176122019-08-30T11:34:43Zcom_10033_620613col_10033_620614
Buchy, Eric
Vukosavljevic, Branko
Windbergs, Maike
Sobot, Dunja
Dejean, Camille
Mura, Simona
Couvreur, Patrick
Desmaële, Didier
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
http://creativecommons.org/licenses/by-nc-sa/4.0/
openAccess
Synthesis of a deuterated probe for the confocal Raman microscopy imaging of squalenoyl nanomedicines
Article
oai:repository.helmholtz-hzi.de:10033/6179852019-09-06T01:30:53Zcom_10033_620613col_10033_620614
Mostaghaci, Babak
Loretz, Brigitta
Lehr, Claus-Michael
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
oai:repository.helmholtz-hzi.de:10033/6186022019-08-30T11:27:16Zcom_10033_620613col_10033_620614
Planz, Viktoria
Seif, Salem
Atchison, Jennifer S
Vukosavljevic, Branko
Sparenberg, Lisa
Kroner, Elmar
Windbergs, Maike
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
oai:repository.helmholtz-hzi.de:10033/6206072018-06-12T17:07:04Zcom_10033_620613col_10033_620614
Hittinger, Marius
Janke, Julia
Huwer, Hanno
Scherließ, Regina
Schneider-Daum, Nicole
Lehr, Claus Michael
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.
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
oai:repository.helmholtz-hzi.de:10033/6205792019-08-30T11:26:42Zcom_10033_620613col_10033_620614
Hittinger, Marius
Janke, Julia
Huwer, Hanno
Scherließ, Regina
Schneider-Daum, Nicole
Lehr, Claus Michael
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.
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
oai:repository.helmholtz-hzi.de:10033/6205802019-08-30T11:26:42Zcom_10033_620613col_10033_620614
Hittinger, Marius
Mell, Nico Alexander
Huwer, Hanno
Loretz, Brigitta
Schneider-Daum, Nicole
Lehr, Claus Michael
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.
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
oai:repository.helmholtz-hzi.de:10033/6205822019-08-30T11:26:13Zcom_10033_620613col_10033_620614
Lerner, Thomas R
de Souza Carvalho-Wodarz, Cristiane
Repnik, Urska
Russell, Matthew R G
Borel, Sophie
Diedrich, Collin R
Rohde, M
Wainwright, Helen
Collinson, Lucy M
Wilkinson, Robert J
Griffiths, Gareth
Gutierrez, Maximiliano G
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.
http://creativecommons.org/licenses/by-nc-sa/4.0/
openAccess
Lymphatic endothelial cells are a replicative niche for Mycobacterium tuberculosis.
Article
oai:repository.helmholtz-hzi.de:10033/6206152019-08-30T11:35:39Zcom_10033_620613col_10033_620614
Thiele, Carolin
Loretz, Brigitta
Lehr, Claus Michael
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.
http://creativecommons.org/licenses/by-nc-sa/4.0/
Biodegradable starch derivatives with tunable charge density-synthesis, characterization, and transfection efficiency.
Article
oai:repository.helmholtz-hzi.de:10033/6208762019-08-30T11:35:39Zcom_10033_620613col_10033_620614
Susewind, Julia
de Souza Carvalho-Wodarz, Cristiane
Repnik, Urska
Collnot, Eva-Maria
Schneider-Daum, Nicole
Griffiths, Gareth Wyn
Lehr, Claus-Michael
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
http://creativecommons.org/licenses/by-nc-sa/4.0/
openAccess
A 3D co-culture of three human cell lines to model the inflamed intestinal mucosa for safety testing of nanomaterials.
Article
oai:repository.helmholtz-hzi.de:10033/6208872019-08-30T11:36:04Zcom_10033_620613col_10033_620614
Pelaz, Beatriz
Alexiou, Christoph
Alvarez-Puebla, Ramon A
Alves, Frauke
Andrews, Anne M
Ashraf, Sumaira
Balogh, Lajos P
Ballerini, Laura
Bestetti, Alessandra
Brendel, Cornelia
Bosi, Susanna
Carril, Monica
Chan, Warren C W
Chen, Chunying
Chen, Xiaodong
Chen, Xiaoyuan
Cheng, Zhen
Cui, Daxiang
Du, Jianzhong
Dullin, Christian
Escudero, Alberto
Feliu, Neus
Gao, Mingyuan
George, Michael
Gogotsi, Yury
Grünweller, Arnold
Gu, Zhongwei
Halas, Naomi J
Hampp, Norbert
Hartmann, Roland K
Hersam, Mark C
Hunziker, Patrick
Jian, Ji
Jiang, Xingyu
Jungebluth, Philipp
Kadhiresan, Pranav
Kataoka, Kazunori
Khademhosseini, Ali
Kopeček, Jindřich
Kotov, Nicholas A
Krug, Harald F
Lee, Dong Soo
Lehr, Claus-Michael
Leong, Kam W
Liang, Xing-Jie
Ling Lim, Mei
Liz-Marzán, Luis M
Ma, Xiaowei
Macchiarini, Paolo
Meng, Huan
Möhwald, Helmuth
Mulvaney, Paul
Nel, Andre E
Nie, Shuming
Nordlander, Peter
Okano, Teruo
Oliveira, Jose
Park, Tai Hyun
Penner, Reginald M
Prato, Maurizio
Puntes, Victor
Rotello, Vincent M
Samarakoon, Amila
Schaak, Raymond E
Shen, Youqing
Sjöqvist, Sebastian
Skirtach, Andre G
Soliman, Mahmoud G
Stevens, Molly M
Sung, Hsing-Wen
Tang, Ben Zhong
Tietze, Rainer
Udugama, Buddhisha N
VanEpps, J Scott
Weil, Tanja
Weiss, Paul S
Willner, Itamar
Wu, Yuzhou
Yang, Lily
Yue, Zhao
Zhang, Qian
Zhang, Qiang
Zhang, Xian-En
Zhao, Yuliang
Zhou, Xin
Parak, Wolfgang J
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
oai:repository.helmholtz-hzi.de:10033/6209182019-08-30T11:27:16Zcom_10033_620613col_10033_620685
Fuhrmann, Gregor
Neuer, Anna Lena
Herrmann, Inge K
2017-05-16T11:07:12Z
2017-05-16T11:07:12Z
2017-04-07
Extracellular vesicles - A promising avenue for the detection and treatment of infectious diseases? 2017 Eur J Pharm Biopharm
1873-3441
28396279
10.1016/j.ejpb.2017.04.005
http://hdl.handle.net/10033/620918
European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V
Extracellular vesicles (EVs) have gained increasing attention as novel disease biomarkers and as promising therapeutic agents. These cell-derived, phospholipid-based particles are present in many - if not all - physiological fluids. They have been shown to govern several physiological processes, such as cell-cell communication, but also to be involved in pathological conditions, for example tumour progression. In infectious diseases, EVs have been shown to induce host immune responses and to mediate transfer of virulence or resistance factors. Here, we discuss recent developments in using EVs as diagnostic tools for infectious diseases, the development of EV-based vaccines and the use of EVs as potential anti-infective entity. We illustrate how EV-based strategies could open a viable new avenue to tackle current challenges in the field of infections, including barrier penetration and growing resistance to antimicrobials.
en
http://creativecommons.org/licenses/by-nc-sa/4.0/
Extracellular vesicles - A promising avenue for the detection and treatment of infectious diseases?
Article
oai:repository.helmholtz-hzi.de:10033/6209242019-08-30T11:33:57Zcom_10033_620613col_10033_620614
Günday Türeli, Nazende
Torge, Afra
Juntke, Jenny
Schwarz, Bianca C
Schneider-Daum, Nicole
Türeli, Akif Emre
Lehr, Claus-Michael
Schneider, Marc
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
oai:repository.helmholtz-hzi.de:10033/6209262019-08-30T11:35:39Zcom_10033_620613col_10033_620614
Nickel, Sabrina
Selo, Mohammed Ali
Fallack, Juliane
Clerkin, Caoimhe G
Huwer, Hanno
Schneider-Daum, Nicole
Lehr, Claus Michael
Ehrhardt, Carsten
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
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Expression and Activity of Breast Cancer Resistance Protein (BCRP/ABCG2) in Human Distal Lung Epithelial Cells In Vitro.
Article
oai:repository.helmholtz-hzi.de:10033/6209322019-08-30T11:33:05Zcom_10033_620613col_10033_620614
Ricci, Francesca
Murgia, Xabier
Razzetti, Roberta
Pelizzi, Nicola
Salomone, Fabrizio
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
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In vitro and in vivo comparison between poractant alfa and the new generation synthetic surfactant CHF5633.
Article
oai:repository.helmholtz-hzi.de:10033/6210122019-08-30T11:25:43Zcom_10033_620613col_10033_620614
Ricci, Francesca
Catozzi, Chiara
Murgia, Xabier
Rosa, Brenda
Amidani, Davide
Lorenzini, Luca
Bianco, Federico
Rivetti, Claudio
Catinella, Silvia
Villetti, Gino
Civelli, Maurizio
Pioselli, Barbara
Dani, Carlo
Salomone, Fabrizio
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
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Physiological, Biochemical, and Biophysical Characterization of the Lung-Lavaged Spontaneously-Breathing Rabbit as a Model for Respiratory Distress Syndrome.
Article
oai:repository.helmholtz-hzi.de:10033/6210142019-08-30T11:34:22Zcom_10033_620613col_10033_620614
Rigo, Lucas A
Carvalho-Wodarz, Cristiane S
Pohlmann, Adriana R
Guterres, Silvia S
Schneider-Daum, Nicole
Lehr, Claus Michael
Beck, Ruy C R
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
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Nanoencapsulation of a glucocorticoid improves barrier function and anti-inflammatory effect on monolayers of pulmonary epithelial cell lines.
Article
oai:repository.helmholtz-hzi.de:10033/6210782019-08-30T11:31:22Zcom_10033_620613col_10033_620614
Loretz, Brigitta
Schneider-Daum, Nicole
Windbergs, Maike
Schaefer, Ulrich
Schneider, Marc
Lehr, Claus Michael
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
en
http://creativecommons.org/licenses/by-nc-sa/4.0/
Barriers and motivations for non-invasive drug delivery.
Editorial
oai:repository.helmholtz-hzi.de:10033/6211432019-08-30T11:34:48Zcom_10033_620613col_10033_620614
Ribeiro, Giovanni Monteiro
Matsumoto, Cristianne Kayoko
Real, Fernando
Teixeira, Daniela
Duarte, Rafael Silva
Mortara, Renato Arruda
Leão, Sylvia Cardoso
de Souza Carvalho-Wodarz, Cristiane
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
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Increased survival and proliferation of the epidemic strain Mycobacterium abscessus subsp. massiliense CRM0019 in alveolar epithelial cells.
Article
oai:repository.helmholtz-hzi.de:10033/6211832019-08-30T11:33:29Zcom_10033_620613col_10033_620614
Andrade, Diego Fontana de
Vukosavljevic, Branko
Benvenutti, Edilson Valmir
Pohlmann, Adriana Raffin
Guterres, Sílvia Stanisçuaski
Windbergs, Maike
Beck, Ruy Carlos Ruver
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
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Redispersible spray-dried lipid-core nanocapsules intended for oral delivery: the influence of the particle number on redispersibility.
Article
oai:repository.helmholtz-hzi.de:10033/6212722019-08-30T11:31:23Zcom_10033_620613col_10033_620614
Serr, Isabelle
Fürst, Rainer W
Ott, Verena B
Scherm, Martin G
Nikolaev, Alexei
Gökmen, Füsun
Kälin, Stefanie
Zillmer, Stephanie
Bunk, Melanie
Weigmann, Benno
Kunschke, Nicole
Loretz, Brigitta
Lehr, Claus Michael
Kirchner, Benedikt
Haase, Bettina
Pfaffl, Michael
Waisman, Ari
Willis, Richard A
Ziegler, Anette-G
Daniel, Carolin
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
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miRNA92a targets KLF2 and the phosphatase PTEN signaling to promote human T follicular helper precursors in T1D islet autoimmunity.
Article
oai:repository.helmholtz-hzi.de:10033/6212872019-08-30T11:33:30Zcom_10033_620613col_10033_620614
Graef, Florian
Vukosavljevic, Branko
Michel, Jean-Philippe
Wirth, Marius
Ries, Oliver
De Rossi, Chiara
Windbergs, Maike
Rosilio, Véronique
Ducho, Christian
Gordon, Sarah
Lehr, Claus Michael
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
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The bacterial cell envelope as delimiter of anti-infective bioavailability - An in vitro permeation model of the Gram-negative bacterial inner membrane.
Article
oai:repository.helmholtz-hzi.de:10033/6213132019-08-30T11:33:30Zcom_10033_620613col_10033_620614
Castoldi, Arianna
Herr, Christian
Niederstraßer, Julia
Labouta, Hagar Ibrahim
Melero, Ana
Gordon, Sarah
Schneider-Daum, Nicole
Bals, Robert
Lehr, Claus Michael
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
oai:repository.helmholtz-hzi.de:10033/6213302019-08-30T11:30:58Zcom_10033_620613col_10033_620614
Serr, Isabelle
Scherm, Martin G
Zahm, Adam M
Schug, Jonathan
Flynn, Victoria K
Hippich, Markus
Kälin, Stefanie
Becker, Maike
Achenbach, Peter
Nikolaev, Alexei
Gerlach, Katharina
Liebsch, Nicole
Loretz, Brigitta
Lehr, Claus Michael
Kirchner, Benedikt
Spornraft, Melanie
Haase, Bettina
Segars, James
Küper, Christoph
Palmisano, Ralf
Waisman, Ari
Willis, Richard A
Kim, Wan-Uk
Weigmann, Benno
Kaestner, Klaus H
Ziegler, Anette-Gabriele
Daniel, Carolin
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
oai:repository.helmholtz-hzi.de:10033/6213442019-08-30T11:35:33Zcom_10033_620613col_10033_620614
Yasar, Hanzey
Ho, Duy-Khiet
De Rossi, Chiara
Herrmann, Jennifer
Gordon, Sarah
Loretz, Brigitta
Lehr, Claus Michael
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://creativecommons.org/licenses/by-nc-sa/4.0/
Starch-Chitosan Polyplexes: A Versatile Carrier System for Anti-Infectives and Gene Delivery
Article
oai:repository.helmholtz-hzi.de:10033/6213522019-08-30T11:33:29Zcom_10033_620613col_10033_620685
Fuhrmann, Gregor
Chandrawati, Rona
Parmar, Paresh A
Keane, Timothy J
Maynard, Stephanie A
Bertazzo, Sergio
Stevens, Molly M
2018-04-13T08:27:37Z
2018-04-13T08:27:37Z
2018-02-23
Engineering Extracellular Vesicles with the Tools of Enzyme Prodrug Therapy. 2018 Adv. Mater. Weinheim
1521-4095
29473230
10.1002/adma.201706616
http://hdl.handle.net/10033/621352
Advanced materials (Deerfield Beach, Fla.)
Extracellular vesicles (EVs) have recently gained significant attention as important mediators of intercellular communication, potential drug carriers, and disease biomarkers. These natural cell-derived nanoparticles are postulated to be biocompatible, stable under physiological conditions, and to show reduced immunogenicity as compared to other synthetic nanoparticles. Although initial clinical trials are ongoing, the use of EVs for therapeutic applications may be limited due to undesired off-target activity and potential "dilution effects" upon systemic administration which may affect their ability to reach their target tissues. To fully exploit their therapeutic potential, EVs are embedded into implantable biomaterials designed to achieve local delivery of therapeutics taking advantage of enzyme prodrug therapy (EPT). In this first application of EVs for an EPT approach, EVs are used as smart carriers for stabilizing enzymes in a hydrogel for local controlled conversion of benign prodrugs to active antiinflammatory compounds. It is shown that the natural EVs' antiinflammatory potential is comparable or superior to synthetic carriers, in particular upon repeated long-term incubations and in different macrophage models of inflammation. Moreover, density-dependent color scanning electron microscopy imaging of EVs in a hydrogel is presented herein, an impactful tool for further understanding EVs in biological settings.
en
http://creativecommons.org/licenses/by-nc-sa/4.0/
Engineering Extracellular Vesicles with the Tools of Enzyme Prodrug Therapy.
Article
oai:repository.helmholtz-hzi.de:10033/6213842019-08-30T11:32:36Zcom_10033_620613col_10033_620614
Metz, Julia
Knoth, Katharina
Groß, Henrik
Lehr, Claus-Michael
Stäbler, Carolin
Bock, Udo
Hittinger, Marius
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.
http://creativecommons.org/licenses/by-nc-sa/3.0/us/
Attribution-NonCommercial-ShareAlike 3.0 United States
Bepanthen® Eye and Nose Ointment
aerosol deposition in vitro system
allergy prevention
nasal mucosa
pollen
Combining MucilAir™ and Vitrocell Powder Chamber for the In Vitro Evaluation of Nasal Ointments in the Context of Aerosolized Pollen.
Article
oai:repository.helmholtz-hzi.de:10033/6214472019-08-30T11:26:10Zcom_10033_620613col_10033_620614
Ernst, Matthias
John, Thomas
Guenther, Marco
Wagner, Christian
Schaefer, Ulrich F
Lehr, Claus-Michael
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
http://creativecommons.org/licenses/by-nc-sa/3.0/us/
Attribution-NonCommercial-ShareAlike 3.0 United States
A Model for the Transient Subdiffusive Behavior of Particles in Mucus.
Article
oai:repository.helmholtz-hzi.de:10033/6214622019-08-30T11:29:14Zcom_10033_620613col_10033_620614
Pontes, Montcharles S.
Montefusco-Pereira, Carlos V.
Misra, Biswapriya B.
Ribeiro-Junior, Howard L.
Graciano, Daniela E.
Santos, Jaqueline S.
Nobrega, Michele A.S.
Fernandes, Shaline S.L.
Caires, Anderson R.L.
Santiago, Etenaldo F.
2018-09-03T08:20:19Z
2018-09-03T08:20:19Z
22143173
10.1016/j.inpa.2018.07.001
http://hdl.handle.net/10033/621462
http://creativecommons.org/licenses/by-nc-sa/3.0/us/
Attribution-NonCommercial-ShareAlike 3.0 United States
High-throughput phenotyping by applying digital morphometrics and fluorescence induction curves in seeds to identifying variations: A case study of Annona (Annonaceae) species
Article
oai:repository.helmholtz-hzi.de:10033/6214822019-11-20T02:02:10Zcom_10033_620613com_10033_620656col_10033_620614col_10033_620685col_10033_620657
Frank, Julia
Richter, Maximilian
de Rossi, Chiara
Lehr, Claus-Michael
Fuhrmann, Kathrin
Fuhrmann, Gregor
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.
http://creativecommons.org/licenses/by-nc-sa/3.0/us/
Attribution-NonCommercial-ShareAlike 3.0 United States
Extracellular vesicles protect glucuronidase model enzymes during freeze-drying.
Article
oai:repository.helmholtz-hzi.de:10033/6215082019-08-30T11:29:45Zcom_10033_620613col_10033_620614
Yasar, Hanzey
Biehl, Alexander
De Rossi, Chiara
Koch, Marcus
Murgia, Xabi
Loretz, Brigitta
Lehr, Claus-Michael
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.
http://creativecommons.org/licenses/by-nc-sa/3.0/us/
Attribution-NonCommercial-ShareAlike 3.0 United States
Cationic lipid
Chitosan-PLGA
Gene delivery
Live cell imaging
Transfection
mRNA
Kinetics of mRNA delivery and protein translation in dendritic cells using lipid-coated PLGA nanoparticles.
Article
oai:repository.helmholtz-hzi.de:10033/6215122018-10-12T12:37:47Zcom_10033_620613col_10033_620614
Metz, Julia
Knoth, Katharina
Groß, Henrik
Lehr, Claus-Michael
Stäbler, Carolin
Bock, Udo
Hittinger, Marius
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
http://creativecommons.org/licenses/by-nc-sa/3.0/us/
Attribution-NonCommercial-ShareAlike 3.0 United States
Bepanthen® Eye and Nose Ointment
aerosol deposition in vitro system
allergy prevention
nasal mucosa
pollen
Combining MucilAir™ and Vitrocell Powder Chamber for the In Vitro Evaluation of Nasal Ointments in the Context of Aerosolized Pollen.
Article
oai:repository.helmholtz-hzi.de:10033/6215142019-08-30T11:29:45Zcom_10033_620613col_10033_620614
Niederstrasser, Julia
Herr, Christian
Wolf, Lisa
Lehr, Claus M
Beisswenger, Christoph
Bals, Robert
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.
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Attribution-NonCommercial-ShareAlike 3.0 United States
Vitamin D Deficiency Does Not Result in a Breach of Host Defense in Murine Models of Pneumonia.
Article
oai:repository.helmholtz-hzi.de:10033/6215422019-08-30T11:30:26Zcom_10033_620613col_10033_620614
Stucki, Janick D
Hobi, Nina
Galimov, Artur
Stucki, Andreas O
Schneider-Daum, Nicole
Lehr, Claus-Michael
Huwer, Hanno
Frick, Manfred
Funke-Chambour, Manuela
Geiser, Thomas
Guenat, Olivier T
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.
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Attribution-NonCommercial-ShareAlike 3.0 United States
Medium throughput breathing human primary cell alveolus-on-chip model.
Article
oai:repository.helmholtz-hzi.de:10033/6215502019-08-30T11:31:43Zcom_10033_620613col_10033_620614
Ricci, Francesca
Casiraghi, Costanza
Storti, Matteo
D'Alò, Francesco
Catozzi, Chiara
Ciccimarra, Roberta
Ravanetti, Francesca
Cacchioli, Antonio
Villetti, Gino
Civelli, Maurizio
Murgia, Xabi
Carnielli, Virgilio
Salomone, Fabrizio
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.
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Attribution-NonCommercial-ShareAlike 3.0 United States
Surfactant replacement therapy in combination with different non-invasive ventilation techniques in spontaneously-breathing, surfactant-depleted adult rabbits.
Article
oai:repository.helmholtz-hzi.de:10033/6216072018-12-05T15:08:05Zcom_10033_620613col_10033_620614
Metz, Julia
Knoth, Katharina
Groß, Henrik
Lehr, Claus-Michael
Stäbler, Carolin
Bock, Udo
Hittinger, Marius
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
http://creativecommons.org/licenses/by-nc-sa/4.0/
Attribution-NonCommercial-ShareAlike 4.0 International
Bepanthen® Eye and Nose Ointment
aerosol deposition in vitro system
allergy prevention
nasal mucosa
pollen
Combining MucilAir™ and Vitrocell Powder Chamber for the In Vitro Evaluation of Nasal Ointments in the Context of Aerosolized Pollen.
Article
oai:repository.helmholtz-hzi.de:10033/6216242019-08-30T11:33:01Zcom_10033_620613col_10033_620614
Haque, A K M Ashiqul
Dewerth, Alexander
Antony, Justin S
Riethmüller, Joachim
Schweizer, Georg R
Weinmann, Petra
Latifi, Ngadhnjim
Yasar, Hanzey
Pedemonte, Nicoletta
Sondo, Elvira
Weidensee, Brian
Ralhan, Anjali
Laval, Julie
Schlegel, Patrick
Seitz, Christian
Loretz, Brigitta
Lehr, Claus-Michael
Handgretinger, Rupert
Kormann, Michael S D
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
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Attribution-NonCommercial-ShareAlike 4.0 International
Chemically modified hCFTR mRNAs recuperate lung function in a mouse model of cystic fibrosis.
Article
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
Empting, Martin
De Rossi, Chiara
Mayr, Karsten
Dersch, Petra
Hartmann, Rolf
Müller, Rolf
Gordon, Sarah
Lehr, Claus-Michael
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.
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AOT-gentamicin
aspherical nanoparticles
bacteriomimetic nanocarriers
intracellular infection
invasin
Aspherical and Spherical InvA497-Functionalized Nanocarriers for Intracellular Delivery of Anti-Infective Agents.
Article
oai:repository.helmholtz-hzi.de:10033/6216652019-08-30T11:34:20Zcom_10033_620613com_10033_620618col_10033_620685col_10033_620619
Schulz, Eilien
Goes, Adriely
Garcia, Ronald
Panter, Fabian
Koch, Marcus
Müller, Rolf
Fuhrmann, Kathrin
Fuhrmann, Gregor
2019-01-22T10:11:45Z
2019-01-22T10:11:45Z
2018-11-28
1873-4995
30292423
10.1016/j.jconrel.2018.09.030
http://hdl.handle.net/10033/621665
Journal of Controlled Release
Up to 25,000 people die each year from resistant infections in Europe alone, with increasing incidence. It is estimated that a continued rise in bacterial resistance by 2050 would lead up to 10 million annual deaths worldwide, exceeding the incidence of cancer deaths. Although the design of new antibiotics is still one way to tackle the problem, pharmaceutical companies investigate far less into new drugs than 30 years ago. Incorporation of antibiotics into nanoparticle drug carriers ("nanoantibiotics") is currently investigated as a promising strategy to make existing antibiotics regain antimicrobial strength and overcome certain types of microbial drug resistance. Many of these synthetic systems enhance the antimicrobial effect of drugs by protecting antibiotics from degradation and reducing their side effects. Nevertheless, they often cannot selectively target pathogenic bacteria and - due to their synthetic origin - may induce side-effects themselves. In this work, we present the characterisation of naturally derived outer membrane vesicles (OMVs) as biocompatible and inherently antibiotic drug carriers. We isolated OMVs from two representative strains of myxobacteria, Cystobacter velatus Cbv34 and Sorangiineae species strain SBSr073, a bacterial order with the ability of lysing other bacterial strains and currently investigated as sources of new secondary metabolites. We investigated the myxobacterias' inherent antibacterial properties after isolation by differential centrifugation and purification by size-exclusion chromatography. OMVs have an average size range of 145-194 nm. We characterised their morphology by electron cryomicroscopy and found that OMVs are biocompatible with epithelial cells and differentiated macrophages. They showed a low endotoxin activity comparable to those of control samples, indicating a low acute inflammatory potential. In addition, OMVs showed inherent stability under different storage conditions, including 4 °C, -20 °C, -80 °C and freeze-drying. OMV uptake in Gram-negative model bacterium Escherichia coli (E. coli) showed similar to better incorporation than liposome controls, indicating the OMVs may interact with model bacteria via membrane fusion. Bacterial uptake correlated with antimicrobial activity of OMVs as measured by growth inhibition of E. coli. OMVs from Cbv34 inhibited growth of E. coli to a comparable extent as the clinically established antibiotic gentamicin. Liquid-chromatography coupled mass spectrometry analyses revealed the presence of cystobactamids in OMVs, inhibitors of bacterial topoisomerase currently studied to treat different Gram-negative and Gram-positive pathogens. This work, may serve as an important basis for further evaluation of OMVs derived from myxobacteria as novel therapeutic delivery systems against bacterial infections.
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Biogenic drug carriers
Electron cryomicroscopy
Extracellular vesicles
Myxobacteria
Nanoantibiotics
Outer membrane vesicles
Biocompatible bacteria-derived vesicles show inherent antimicrobial activity.
Article
oai:repository.helmholtz-hzi.de:10033/6216692019-08-30T11:24:29Zcom_10033_620613col_10033_620685
Théry, Clotilde
Witwer, Kenneth W
Aikawa, Elena
Alcaraz, Maria Jose
Anderson, Johnathon D
Andriantsitohaina, Ramaroson
Antoniou, Anna
Arab, Tanina
Archer, Fabienne
Atkin-Smith, Georgia K
Ayre, D Craig
Bach, Jean-Marie
Bachurski, Daniel
Baharvand, Hossein
Balaj, Leonora
Baldacchino, Shawn
Bauer, Natalie N
Baxter, Amy A
Bebawy, Mary
Beckham, Carla
Bedina Zavec, Apolonija
Benmoussa, Abderrahim
Berardi, Anna C
Bergese, Paolo
Bielska, Ewa
Blenkiron, Cherie
Bobis-Wozowicz, Sylwia
Boilard, Eric
Boireau, Wilfrid
Bongiovanni, Antonella
Borràs, Francesc E
Bosch, Steffi
Boulanger, Chantal M
Breakefield, Xandra
Breglio, Andrew M
Brennan, Meadhbh Á
Brigstock, David R
Brisson, Alain
Broekman, Marike LD
Bromberg, Jacqueline F
Bryl-Górecka, Paulina
Buch, Shilpa
Buck, Amy H
Burger, Dylan
Busatto, Sara
Buschmann, Dominik
Bussolati, Benedetta
Buzás, Edit I
Byrd, James Bryan
Camussi, Giovanni
Carter, David RF
Caruso, Sarah
Chamley, Lawrence W
Chang, Yu-Ting
Chen, Chihchen
Chen, Shuai
Cheng, Lesley
Chin, Andrew R
Clayton, Aled
Clerici, Stefano P
Cocks, Alex
Cocucci, Emanuele
Coffey, Robert J
Cordeiro-da-Silva, Anabela
Couch, Yvonne
Coumans, Frank AW
Coyle, Beth
Crescitelli, Rossella
Criado, Miria Ferreira
D’Souza-Schorey, Crislyn
Das, Saumya
Datta Chaudhuri, Amrita
de Candia, Paola
De Santana, Eliezer F
De Wever, Olivier
del Portillo, Hernando A
Demaret, Tanguy
Deville, Sarah
Devitt, Andrew
Dhondt, Bert
Di Vizio, Dolores
Dieterich, Lothar C
Dolo, Vincenza
Dominguez Rubio, Ana Paula
Dominici, Massimo
Dourado, Mauricio R
Driedonks, Tom AP
Duarte, Filipe V
Duncan, Heather M
Eichenberger, Ramon M
Ekström, Karin
EL Andaloussi, Samir
Elie-Caille, Celine
Erdbrügger, Uta
Falcón-Pérez, Juan M
Fatima, Farah
Fish, Jason E
Flores-Bellver, Miguel
Försönits, András
Frelet-Barrand, Annie
2019-01-29T09:38:22Z
2019-01-29T09:38:22Z
2001-3078
10.1080/20013078.2018.1535750
http://hdl.handle.net/10033/621669
http://creativecommons.org/licenses/by-nc-sa/4.0/
Attribution-NonCommercial-ShareAlike 4.0 International
Minimal information for studies of extracellular vesicles 2018 (MISEV2018): a position statement of the International Society for Extracellular Vesicles and update of the MISEV2014 guidelines
Article
oai:repository.helmholtz-hzi.de:10033/6217372019-08-30T11:29:41Zcom_10033_620613col_10033_620614
Nnamani, Petra
Ugwu, Agatha
Ibezim, Emmanuel
Onoja, Simon
Odo, Amelia
Windbergs, Maike
Rossi, Chiara
Lehr, Claus-Michael
Attama, Anthony
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.
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Inhibition zone diameter
antimicrobial activity
ciprofloxacin
nanostructured lipid carriers
Preparation, characterisation and in vitro antibacterial property of ciprofloxacin-loaded nanostructured lipid carrier for treatment of Bacillus subtilis infection.
Article
oai:repository.helmholtz-hzi.de:10033/6217642019-08-30T11:35:08Zcom_10033_620613col_10033_620614
Murgia, Xabier
Loretz, Brigitta
Hartwig, Olga
Hittinger, Marius
Lehr, Claus-Michael
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
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Hydrogel
Mucins
Mucoadhesion
Mucopenetration
Mucosal drug delivery
Nanoparticles
PEGylation
Rheology
The role of mucus on drug transport and its potential to affect therapeutic outcomes.
Article
oai:repository.helmholtz-hzi.de:10033/6217732019-08-30T11:28:45Zcom_10033_620613col_10033_620614
Kletting, Stephanie
Barthold, Sarah
Repnik, Urska
Griffiths, Gareth
Loretz, Brigitta
Schneider-Daum, Nicole
de Souza Carvalho-Wodarz, Cristiane
Lehr, Claus-Michael
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.
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Attribution-NonCommercial-ShareAlike 4.0 International
In vitro model
air-blood barrier
nanoparticles
nanotoxicology
pulmonary drug delivery
Co-culture of human alveolar epithelial (hAELVi) and macrophage (THP-1) cell lines.
Article
oai:repository.helmholtz-hzi.de:10033/6219022019-08-30T11:26:11Zcom_10033_620613col_10033_620614
Menina, Sara
Eisenbeis, Janina
Kamal, Mohamed Ashraf M
Koch, Marcus
Bischoff, Markus
Gordon, Sarah
Loretz, Brigitta
Lehr, Claus-Michael
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.
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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
oai:repository.helmholtz-hzi.de:10033/6219362019-09-14T01:29:41Zcom_10033_620613col_10033_620614
Artzy-Schnirman, Arbel
Hobi, Nina
Schneider-Daum, Nicole
Guenat, Olivier T
Lehr, Claus-Michael
Sznitman, Josué
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"
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embargoedAccess
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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
oai:repository.helmholtz-hzi.de:10033/6219372019-09-14T01:29:40Zcom_10033_620613col_10033_620614
Ho, Duy-Khiet
Nichols, Brittany L B
Edgar, Kevin J
Murgia, Xabier
Loretz, Brigitta
Lehr, Claus-Michael
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.
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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
oai:repository.helmholtz-hzi.de:10033/6219422019-09-17T02:31:02Zcom_10033_620613com_10033_620601col_10033_620614col_10033_620602
Durán, Verónica
Yasar, Hanzey
Becker, Jennifer
Thiyagarajan, Durairaj
Loretz, Brigitta
Kalinke, Ulrich
Lehr, Claus-Michael
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.
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Attribution-NonCommercial-ShareAlike 4.0 International
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
oai:repository.helmholtz-hzi.de:10033/6219442019-09-18T03:36:38Zcom_10033_620613com_10033_620601col_10033_620614col_10033_620602
Salomon, Johanna J.
Gausterer, Julia C.
Selo, Mohammed Ali
Hosoya, Ken Ichi
Huwer, Hanno
Schneider-Daum, Nicole
Lehr, Claus Michael
Ehrhardt, Carsten
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.
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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
oai:repository.helmholtz-hzi.de:10033/6219872019-10-22T01:38:55Zcom_10033_620613col_10033_620685
Labib, Rola M
Ayoub, Iriny M
Michel, Haidy E
Mehanny, Mina
Kamil, Verena
Hany, Meryl
Magdy, Mirette
Moataz, Aya
Maged, Boula
Mohamed, Ahmed
2019-10-21T13:42:59Z
2019-10-21T13:42:59Z
2019-01-01
PLoS One. 2019 Sep 16;14(9):e0219561. doi: 10.1371/journal.pone.0219561. eCollection 2019.
1932-6203
31525200
10.1371/journal.pone.0219561
http://hdl.handle.net/10033/621987
PLOS ONE
The present study investigates the wound healing potential of three chitosan-based topical preparations loaded with either tea tree essential oil, rosemary essential oil or a mixture of both oils in vivo. Essential oils of M. alternifolia and R. officinalis were analyzed using GC/MS. Essential oil-loaded chitosan topical preparations were formulated. Wound healing potential was evaluated in vivo using an excision wound model in rats. GC/MS analysis of M. alternifolia and R. officinalis essential oils revealed richness in oxygenated monoterpenes, representing 51.06% and 69.61% of the total oil composition, respectively. Topical application of chitosan-based formulation loaded with a mixture of tea tree and rosemary oils resulted in a significant increase in wound contraction percentage compared to either group treated with individual essential oils and the untreated group. Histopathological examination revealed that topical application of tea tree and rosemary oil combination demonstrated complete re-epithelialization associated with activated hair follicles. The high percentage of oxygenated monoterpenes in both essential oils play an important role in the antioxidant and wound healing potential observed herein. Incorporation of tea tree and rosemary essential oils in chitosan-based preparations in appropriate combination could efficiently promote different stages of wound healing.
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Appraisal on the wound healing potential of Melaleuca alternifolia and Rosmarinus officinalis L. essential oil-loaded chitosan topical preparations.
Article
oai:repository.helmholtz-hzi.de:10033/6219902021-07-23T11:19:09Zcom_10033_620613col_10033_620614
Artzy-Schnirman, Arbel
Zidan, Hikaia
Elias-Kirma, Shani
Ben-Porat, Lee
Tenenbaum-Katan, Janna
Carius, Patrick
Fishler, Ramy
Schneider-Daum, Nicole
Lehr, Claus Michael
Sznitman, Josué
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
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embargoedAccess
Attribution-NonCommercial-ShareAlike 4.0 International
epithelial barrier
in vitro assays
microfluidics
organ-on-chip
pulmonary infection
Capturing the Onset of Bacterial Pulmonary Infection in Acini-On-Chips
Article
oai:repository.helmholtz-hzi.de:10033/6220222019-11-21T02:06:58Zcom_10033_620613col_10033_620614
Formicola, Beatrice
Dal Magro, Roberta
Montefusco-Pereira, Carlos V
Lehr, Claus-Michael
Koch, Marcus
Russo, Laura
Grasso, Gianvito
Deriu, Marco A
Danani, Andrea
Bourdoulous, Sandrine
Re, Francesca
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
http://creativecommons.org/licenses/by-nc-sa/4.0/
Attribution-NonCommercial-ShareAlike 4.0 International
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
oai:repository.helmholtz-hzi.de:10033/6220392019-12-06T02:03:50Zcom_10033_620613col_10033_620685
Woith, Eric
Fuhrmann, Gregor
Melzig, Matthias F
2019-12-05T09:06:17Z
2019-12-05T09:06:17Z
2019-11-14
Int J Mol Sci. 2019 Nov 14;20(22). pii: ijms20225695. doi: 10.3390/ijms20225695.
1422-0067
31739393
10.3390/ijms20225695
http://hdl.handle.net/10033/622039
International Journal of Molecular Sciences
It is known that extracellular vesicles (EVs) are shed from cells of almost every type of cell or organism, showing their ubiquity in all empires of life. EVs are defined as naturally released particles from cells, delimited by a lipid bilayer, and cannot replicate. These nano- to micrometer scaled spheres shuttle a set of bioactive molecules. EVs are of great interest as vehicles for drug targeting and in fundamental biological research, but in vitro culture of animal cells usually achieves only small yields. The exploration of other biological kingdoms promises comprehensive knowledge on EVs broadening the opportunities for basic understanding and therapeutic use. Thus, plants might be sustainable biofactories producing nontoxic and highly specific nanovectors, whereas bacterial and fungal EVs are promising vaccines for the prevention of infectious diseases. Importantly, EVs from different eukaryotic and prokaryotic kingdoms are involved in many processes including host-pathogen interactions, spreading of resistances, and plant diseases. More extensive knowledge of inter-species and interkingdom regulation could provide advantages for preventing and treating pests and pathogens. In this review, we present a comprehensive overview of EVs derived from eukaryota and prokaryota and we discuss how better understanding of their intercommunication role provides opportunities for both fundamental and applied biology.
en
http://creativecommons.org/licenses/by-nc-sa/4.0/
Attribution-NonCommercial-ShareAlike 4.0 International
archaea
cross-kingdom RNAi
eukaryota
extracellular vesicles
interkingdom communication
prokaryota
Extracellular Vesicles-Connecting Kingdoms.
Review
oai:repository.helmholtz-hzi.de:10033/6220592020-01-04T02:02:30Zcom_10033_620613com_10033_620618col_10033_620614col_10033_620619
Anversa Dimer, Frantiescoli
de Souza Carvalho-Wodarz, Cristiane
Goes, Adriely
Cirnski, Katarina
Herrmann, Jennifer
Schmitt, Viktoria
Pätzold, Linda
Abed, Nadia
de Rossi, Chiara
Bischoff, Markus
Couvreur, Patrick
Müller, Rolf
Lehr, Claus-Michael
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
http://creativecommons.org/licenses/by-nc-sa/4.0/
Attribution-NonCommercial-ShareAlike 4.0 International
Clarithromycin
Mycobacterium abscessus
Nanoparticle
Permeability
Staphylococcus aureus
PLGA nanocapsules improve the delivery of clarithromycin to kill intracellular Staphylococcus aureus and Mycobacterium abscessus.
Article
oai:repository.helmholtz-hzi.de:10033/6220602020-01-04T02:02:30Zcom_10033_620613col_10033_620685
Schulz, Eilien
Karagianni, Anna
Koch, Marcus
Fuhrmann, Gregor
2020-01-03T14:06:40Z
2020-01-03T14:06:40Z
2019-12-02
Eur J Pharm Biopharm. 2019 Dec 2. pii: S0939-6411(19)31309-8. doi: 10.1016/j.ejpb.2019.11.010.
1873-3441
31805356
10.1016/j.ejpb.2019.11.010
http://hdl.handle.net/10033/622060
European Journal of Pharmaceutics and Biopharmaceutics
In recent years, extracellular vesicles (EVs) and outer membrane vesicles (OMVs) have become an extensive and diverse field of research. They hold potential as diagnostic markers, therapeutics and for fundamental biological understanding. Despite ongoing studies, numerous information regarding function, content and stability of EVs remains unclear. If EVs and OMVs ought to be used as therapeutics and in clinical environments, their stability is one of the most important factors to be considered. Especially for formulation development, EVs and OMVs need to be stable at higher temperatures. To the best of our knowledge, very little work has been published regarding heat stability of neither EVs nor OMVs. In the present study, we investigated B lymphoblastoid cell-derived EVs and OMVs derived from myxobacterial species Sorangiineae as model vesicles. We exposed the vesicles to 37 °C, 50 °C, 70 °C and 100 °C for 1 h, 6 h and 24 h, and also autoclaved them. Interestingly, physico-chemical analyses such as size, particle concentration and protein concentration showed minor alterations, particularly at 37 °C. Flow cytometry analysis emphasised these results suggesting that after heat impact, EVs and OMVs were still able to be taken up by macrophage-like dTHP-1 cells. These data indicate that both mammalian and bacterial vesicles show intrinsic stability at physiological temperature. Our findings are important to consider for vesicle formulation and for advanced bioengineering approaches.
en
http://creativecommons.org/licenses/by-nc-sa/4.0/
Attribution-NonCommercial-ShareAlike 4.0 International
autoclaving
drug carriers
extracellular vesicles
flow cytometry
heat stability
lymphoblastoid cells
myxobacteria
outer membrane vesicles
Hot EVs - how temperature affects extracellular vesicles.
Article
mods///com_10033_620613/100