Preclinical testing of dendritic core-multishell nanoparticles in inflammatory skin equivalents

Item Type:	Article
Title:	Preclinical testing of dendritic core-multishell nanoparticles in inflammatory skin equivalents
Creators Name:	Graff, P. and Hönzke, S. and Joshi, A.A. and Yealland, G. and Fleige, E. and Unbehauen, M. and Schäfer-Korting, M. and Hocke, A. and Haag, R. and Hedtrich, S.
Abstract:	Human skin equivalents emerged as novel tools in preclinical dermatological research. It is being claimed that they may bridge the translational gap between preclinical and clinical research, yet only a few studies have investigated their suitability for preclinical drug testing so far. Therefore, we investigated if inflammatory skin equivalents, which emulate hallmarks of atopic dermatitis (AD), are suitable to assess the anti-inflammatory effects of dexamethasone (DXM) in a cream formulation or loaded onto dendritic core-multishell nanoparticles. Topical DXM application resulted in significantly decreased expression of the proinflammatory cytokine TSLP, increased expression of the skin barrier protein involucrin, and facilitated glucocorticoid receptor translocation in a dose-dependent manner. Further, DXM treatment inhibited gene expression of extracellular matrix components, potentially indicative of the known skin atrophy-inducing side effects of glucocorticoids. Overall, we were able to successfully assess the anti-inflammatory effects of DXM and the superiority of the nanoparticle formulation. Nevertheless the identification of robust readout parameters proved challenging and requires careful study design.
Keywords:	Topical Drug Delivery, Nanoparticles, Skin Equivalents, Glucocorticoids, Atopic Dermatitis, Dexamethasone
Source:	Molecular Pharmaceutics
ISSN:	1543-8392
Publisher:	American Chemical Society
Volume:	19
Number:	6
Page Range:	1795-1802
Date:	6 June 2022
Official Publication:	https://doi.org/10.1021/acs.molpharmaceut.1c00734
PubMed:	View item in PubMed

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