Preclinical Testing of Dendritic Core-Multishell Nanoparticles in Inflammatory Skin Equivalents br

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.