Accelerating topical formulation development for inflammatory dermatoses; an ex vivo human skin culture model consistent with clinical therapeutics

Neil, J. E., Brown, M. B., Lenn, J. D. and Williams, A. C. ORCID: https://orcid.org/0000-0003-3654-7916 (2022) Accelerating topical formulation development for inflammatory dermatoses; an ex vivo human skin culture model consistent with clinical therapeutics. International Journal of Pharmaceutics, 618. p. 121648. ISSN 0378-5173 doi: 10.1016/j.ijpharm.2022.121648

Abstract/Summary

Although animal models have been extensively used to evaluate human topical therapeutics, they exhibit marked physiological differences to human skin. 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. Ex vivo skin barrier integrity and metabolic activity was retained for 5 days and stimulation of T-helper cells (Th1), which produce proinflammatory cytokines, provided inflammatory responses similar to those reported from in vivo biopsy. Tissue responses to established therapies of pimecrolimus (Elidel) and clobetasol propionate (Dermovate) were evaluated using the human ex vivo skin culture, assessing pharmacodynamic changes in gene expression alongside the pharmacokinetics of drug penetration with both products showing time dependent efficacies. The translational utility of the human ex vivo skin culture model of inflammatory dermatoses was demonstrated through comparison with an in vivo clinical study, with similar reductions in inflammatory gene expression recorded for both drug treatments. Thus, this model can reduce, replace or refine animal testing and also mitigate the risk of failure in costly and time-consuming clinical trials associated with novel topical therapeutic development.

Item Type	Article
URI	https://reading-clone.eprints-hosting.org/id/eprint/104137
Item Type	Article
Refereed	Yes
Divisions	Life Sciences > School of Chemistry, Food and Pharmacy > School of Pharmacy > Pharmaceutics Research Group
Publisher	Elsevier
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