The current study focused on the development of an ex vivo human skin model to investigate the added value of nanoparticle-based drug delivery systems on skin penetration and drug-mediated efficacy compared to conventional drug formulations for the topical therapy of inflammatory skin diseases. In order to induce different types and intensities of skin barrier disruption, physical and chemical means were applied on human skin explants obtained from plastic surgery. Comparative studies on

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... ral integrity, biophysical parameters and cytokine levels were performed three times within 48 hours in two culture systems of skin. Cultures of skin maintained in tissue media preserved key skin barrier parameters and viability better than medium-free cultures in humidified chambers. The standardization of 50-times tape stripping and 4-hour sodium lauryl sulfate (5% w/v) pretreatment was reliable: transepidermal water loss values and interleukin-6 /-8 levels as examples of a wide range of affected inflammatory mediators were increased reproducibly compared to intact skin. Different structural and biological changes were induced, which are usually associated with pathological changes in diseased skin. Transepidermal water loss measurements provide a noninvasive screening tool to control and standardize skin barrier disruption ex vivo. Based on these results, time- and tissue-sparing protocols and methods for further investigations were adapted to a short-term skin culture system. Intradermal microdialysis in one experimental setup including up to nine sets for up to 24 hours enabled comparison of intact versus physically and chemically barrier-disrupted skin on the skin of one donor as well as three dexamethasone formulations (ethyl cellulose nanocarriers, nanocrystals and a conventional cream) in parallel. The application of highly sensitive detection methods, such as liquid-chromatography-tandem-mass spectrometry and Luminex R multiplex technology, provided a complex set of data on skin penetration and biological effects [...]