A new ex vivo skin model for mechanistic understanding of putative anti-inflammatory topical therapeutics

Neil, M. S. J. E., Lenn, J. D., Brown, M. B. and Williams, A. C. ORCID: https://orcid.org/0000-0003-3654-7916 (2022) A new ex vivo skin model for mechanistic understanding of putative anti-inflammatory topical therapeutics. International Journal of Pharmaceutics, 617. 121610. ISSN 0378-5173 doi: 10.1016/j.ijpharm.2022.121610

Abstract/Summary

Several in vitro models have been designed as test systems for inflammatory skin conditions, commonly using cell-culture or reconstructed human epidermis approaches. However, these systems poorly recapitulate the physiology and, importantly, the metabolism and biochemical activity of skin in vivo, whereas ex vivo skin culture models can retain these features of the tissue. Our objective was to develop a human ex vivo skin culture model to explore the pathophysiology of inflammatory dermatoses and for preclinical testing of potential therapeutic treatments. Following exogenous stimulation, tissue integrity and ability to induce inflammatory gene expression was retained, and stimulant concentrations and duration was optimised to mimic published data from inflammatory clinical biopsies of dermatitis and psoriasis patients. The validity and utility of the model was demonstrated when challenged with 5 drugs including a corticosteroid and vitamin D3 analogue, where inflammatory biomarkers were regulated in a manner consistent with the drugs’ reported in vivo mechanisms of action. This model retains important inflammatory gene signals observed in human inflammatory dermatoses for preclinical evaluation of novel therapeutics.

Item Type	Article
URI	https://reading-clone.eprints-hosting.org/id/eprint/103845
Identification Number/DOI	10.1016/j.ijpharm.2022.121610
Refereed	Yes
Divisions	Life Sciences > School of Chemistry, Food and Pharmacy > School of Pharmacy > Pharmaceutics Research Group
Publisher	Elsevier
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