Liposome-Mediated Transdermal Delivery of Neferine for Enhanced Protection Against Skin Photoaging

Chronic ultraviolet (UV) irradiation-induced skin photoaging is driven by oxidative stress, extracellular matrix degradation, and cellular senescence. To overcome the poor skin permeability and rapid clearance of neferine (Nef), PEGylated liposomes were prepared via thin-film hydration. The Nef-loaded liposomes (Lipo) were spherical, with a mean diameter of 137.90 ± 0.56 nm, a PDI of 0.117 ± 0.016, an encapsulation efficiency of 68.79% ± 1.01%, and a drug loading of 13.38% ± 0.22%. Ex vivo Franz diffusion cell assays demonstrated significantly higher cumulative transdermal permeation over 24 h for Lipo compared with free Nef, along with sustained-release behavior. In a chronic UVA-induced mouse photoaging model, epidermal thickness, dermal collagen networks, and fibroblast mitochondrial ultrastructure were restored by topical Lipo application, with superior effects over free Nef. In UVA-irradiated human dermal fibroblasts, senescence-associated β-galactosidase activity was reduced, intracellular ROS accumulation was eliminated, and SOD activity was restored by the treatment of Lipo. These redox modulations were associated with downregulation of the p53/p21 senescence signaling pathway. Collectively, the antioxidant and anti-senescence efficacy of Nef was enhanced by this liposomal nanoencapsulation strategy through improved transdermal kinetics and cellular responses, providing a functionalized nanoplatform for localized anti-photoaging therapy.