Abstract
Ultraviolet (UV) radiation-induced skin photoaging impacts both appearance and skin health, potentially leading to disorders and cancer. Unlike traditional sunscreens, natural antioxidants can target photoaging at its source. Among these, cathelicidins have attracted considerable research interest due to their multifunctional properties. This study examines the gecko-derived cathelicidin-modified peptide G3CY-10, utilizing a microemulsion gel delivery system to address the challenges related to the transdermal absorption of macromolecular peptides, and systematically assesses its anti-photoaging effects and underlying mechanisms. The results demonstrate that the G3CY-10 microemulsion, formulated with a lecithin-ethanol-butyl acetate system (km = 1:1), exhibits notable stability, and the gelation significantly enhances the transdermal delivery efficiency of G3CY-10. The anti-photoaging efficacy of the G3CY-10 microemulsion gel is substantiated by its capacity to mitigate UV-induced skin photoaging in murine models. This is evidenced by a decrease in epidermal thickness, suppression of sebaceous gland proliferation, and restoration of collagen fiber density. Masson staining further corroborates a significant reduction in collagen degradation. Mechanistic analyses suggest that G3CY-10 primarily confers protection by inhibiting UV-induced collagen degradation and reversing the depletion of superoxide dismutase. This study provides a theoretical foundation and technical support for the clinical translation of natural peptides and the development of innovative anti-photoaging products.