Breaching the Skin Barrier: Efficient Transdermal Delivery of Natural Collagen for Aging Skin Rejuvenation

The supplementation of exogenous collagen is an effective strategy for combating skin aging─a complex physiological process characterized by the continuous degradation of endogenous collagen─its therapeutic efficacy has been severely limited due to poor transdermal permeability. In this study, we developed a novel noninvasive transdermal delivery system (Rh2-CLs) that effectively and safely delivers natural collagen via a novel liposome formulation for aging skin rejuvenation. The permeability of collagen was significantly enhanced by the encapsulation in the optimized liposomes, demonstrating a more than 4-fold improvement in transdermal delivery efficiency compared to free collagen. Circular dichroism spectroscopy confirmed that the encapsulation of liposomes did not disrupt the integrity of the collagen triple-helical structure, thus maintaining its original bioactivity. In a photoaged mouse model, the topical application of Rh2-CLs markedly reduced skin wrinkling and improved skin elasticity. Histological assessments revealed that Rh2-CLs effectively alleviated UV-induced damage and promoted the rapid restoration of skin structure and function through the supplementation and induction of collagen regeneration. In summary, the ginsenoside Rh2-based liposome platform offers a safe, efficient, and noninvasive strategy for transdermal collagen delivery, demonstrating considerable potential for applications in skin regeneration and cosmetic dermatology.