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Graff, P; Honzke, S; Joshi, AA; Yealland, G; Fleige, E; Unbehauen, M; Schafer-Korting, M; Hocke, A; Haag, R; Hedtrich, S.
Preclinical Testing of Dendritic Core-Multishell Nanoparticles in Inflammatory Skin Equivalents br
MOL PHARMACEUT. 2022; 19(6): 1795-1802.
Doi: 10.1021/acs.molpharmaceut.1c00734
Web of Science
PubMed
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- Co-authors Med Uni Graz
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Joshi Aaroh Anand
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- Abstract:
- Human skin equivalents emerged as novel tools inpreclinical dermatological research. It is being claimed that theymay bridge the translational gap between preclinical and clinicalresearch, yet only a few studies have investigated their suitabilityfor preclinical drug testing so far. Therefore, we investigated ifinflammatory skin equivalents, which emulate hallmarks of atopicdermatitis (AD), are suitable to assess the anti-inflammatory effectsof dexamethasone (DXM) in a cream formulation or loaded ontodendritic core-multishell nanoparticles. Topical DXM applicationresulted in significantly decreased expression of the proinflamma-tory cytokine TSLP, increased expression of the skin barrierprotein involucrin, and facilitated glucocorticoid receptor trans-location in a dose-dependent manner. Further, DXM treatmentinhibited gene expression of extracellular matrix components, potentially indicative of the known skin atrophy-inducing side effectsof glucocorticoids. Overall, we were able to successfully assess the anti-inflammatory effects of DXM and the superiority of thenanoparticle formulation. Nevertheless the identification of robust readout parameters proved challenging and requires careful studydesign.
- Find related publications in this database (Keywords)
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topical drug delivery
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nanoparticles
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skin equivalents
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glucocorticoids
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atopic dermatitis
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dexamethasone