ArticleSkin pharmacology and physiology2026
Imaging Active Drug Transport in Viable Human Skin: A Functional ex vivo Skin Model for Mechanistic and Regulatory Applications.
Article in Skin pharmacology and physiology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
introductionUnderstanding drug diffusion and active transport in the viable epidermis (VE) is critical for optimizing topical and transdermal drug delivery. However, the VE remains understudied due to challenges in isolating physiologically intact membranes and limited functional data on cutaneous transporters. This study aimed to develop and validate a viable human epidermal model to assess molecular diffusion and transporter activity using high-resolution imaging, with a focus on P-glycoprotein (P-gp)-mediated transport.
methodsViable epidermis was enzymatically separated from dermatomed human skin using dispase II. Tissue viability was confirmed by MPT-FLIM, MTT assay, and H&E staining. Multiphoton microscopy (MPM) was employed to visualize the diffusion of rhodamine 123 (RD123), a fluorescent P-gp substrate, in dispase-separated epidermis (DSE), and heat-separated epidermis (HSE). The influence of P-gp was evaluated by pretreatment with verapamil, a known inhibitor. ImageJ and MATLAB were used for quantitative image analysis.
resultsRD123 diffusion was faster and more extensive in verapamil-treated DSE, with increased fluorescence intensity in the basal and suprabasal layers at early time points compared to controls. HSE exhibited significantly reduced fluorescence and compromised cellular architecture. MPT-FLIM analysis confirmed that the average NAD(P)H fluorescence lifetime and a
conclusionThis study establishes a viable, structurally intact epidermal model suitable for evaluating both passive and active transport in human skin. Functional imaging confirmed the role of P-gp in modulating drug diffusion across the VE. This platform supports the generation of mechanistic data for improving dermal pharmacokinetic models and has translational relevance for formulation design and regulatory assessment of topical therapies.
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