Nanocarriers for optimizing the balance between interfollicular permeation and follicular uptake of topically applied clobetasol to minimize adverse effects.

2.50
Hdl Handle:
http://hdl.handle.net/10033/599290
Title:
Nanocarriers for optimizing the balance between interfollicular permeation and follicular uptake of topically applied clobetasol to minimize adverse effects.
Authors:
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
Abstract:
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.
Affiliation:
Helmholtz Institute for Pharmaceutical Research Saarland (HIPS);Saarland University, Building A4.1, 66123 Saarbruecken, Germany.
Citation:
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
Journal:
Journal of controlled release : official journal of the Controlled Release Society
Issue Date:
10-Feb-2016
URI:
http://hdl.handle.net/10033/599290
DOI:
10.1016/j.jconrel.2015.12.010
PubMed ID:
26686081
Type:
Article
Language:
en
ISSN:
1873-4995
Appears in Collections:
publications of the department drug delivery ([TC] DDEL)

Full metadata record

DC FieldValue Language
dc.contributor.authorMathes, Cen
dc.contributor.authorMelero, Aen
dc.contributor.authorConrad, Pen
dc.contributor.authorVogt, Ten
dc.contributor.authorRigo, Len
dc.contributor.authorSelzer, Den
dc.contributor.authorPrado, W Aen
dc.contributor.authorDe Rossi, Cen
dc.contributor.authorGarrigues, T Men
dc.contributor.authorHansen, Sen
dc.contributor.authorGuterres, S Sen
dc.contributor.authorPohlmann, A Ren
dc.contributor.authorBeck, R C Ren
dc.contributor.authorLehr, C-Men
dc.contributor.authorSchaefer, U Fen
dc.date.accessioned2016-02-26T15:11:24Zen
dc.date.available2016-02-26T15:11:24Zen
dc.date.issued2016-02-10en
dc.identifier.citationNanocarriers for optimizing the balance between interfollicular permeation and follicular uptake of topically applied clobetasol to minimize adverse effects. 2016, 223:207-14 J Control Releaseen
dc.identifier.issn1873-4995en
dc.identifier.pmid26686081en
dc.identifier.doi10.1016/j.jconrel.2015.12.010en
dc.identifier.urihttp://hdl.handle.net/10033/599290en
dc.description.abstractThe 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
dc.language.isoenen
dc.titleNanocarriers for optimizing the balance between interfollicular permeation and follicular uptake of topically applied clobetasol to minimize adverse effects.en
dc.typeArticleen
dc.contributor.departmentHelmholtz Institute for Pharmaceutical Research Saarland (HIPS);Saarland University, Building A4.1, 66123 Saarbruecken, Germany.en
dc.identifier.journalJournal of controlled release : official journal of the Controlled Release Societyen

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