Background: Ultraviolet (UV) exposure is the predominant cause of skin aging. A systematic evaluation of drug skin permeation via photoaged skin is lacking. Objectives: The aim of this work was to investigate whether UVA and UVB affect absorption by the skin of drugs and sunscreens, including tetracycline, quercetin, and oxybenzone. Methods: The dorsal skin of nude mice was subjected to UVA (24 and 39J/cm2) or UVB (150, 200, and 250mJ/cm2) irradiation. Levels of skin water loss, erythema, and sebum were evaluated, and histological examinations of COX-2 and claudin-1 expressions were carried out. Permeation of the permeants into and through the skin was determined in vitro using a Franz cell. In vivo skin uptake was also evaluated. Senescent skin (24 weeks old) was used for comparison. Results: Wrinkling and scaling were significant signs of skin treated with UVA and UVB, respectively. The level of claudin-1, an indicator of tight junctions (TJs), was reduced by UVA and UVB irradiation. UVA enhanced tetracycline and quercetin skin deposition by 11- and 2-fold, respectively. A similar enhancement was shown for flux profiles. Surprisingly, a lower UVA dose revealed greater enhancement compared to the higher dose. The skin deposition and flux of tetracycline both decreased with UVB exposure. UVB also significantly reduced quercetin flux. The skin absorption behavior of chronologically aged skin approximated that of the UVA group, with photoaged skin showing higher enhancement. UV generally exhibited a negligible effect on modulating oxybenzone permeation. Conclusions: Skin disruption produced by UV does not necessarily result in enhanced skin absorption. It depends on the UV wavelength, irradiated energy, and physicochemical properties of the permeant. To the best of our knowledge, this is the first report establishing drug permeation profiles for UV-irradiated skin.
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