Stabilizing Oroxylin A Transfersomes by Caffeic Acid-Chitosan Functionalization for Superior Photoaging Protection.

Ultraviolet (UV)-radiation-induced intracellular oxidative stress is a key mechanism driving skin photoaging. Nanodelivery systems employed to alleviate photoaging of the skin have been hindered in clinical application due to their inherent instability and functional limitations. To address this issue, we prepared caffeic acid-grafted chitosan (CA-g-CS). Subsequently, oroxylin A-loaded transfersomes were modified with CA-g-CS to obtain CA-g-CS-coated oroxylin A-loaded transfersomes (CA-g-CS-OA-TFs). In vitro studies demonstrated that this system significantly enhanced the transferosome stability and produced a synergistic antioxidant effect. The modification of CA-g-CS markedly suppressed lipid oxidation, increasing the DPPH and ABTS radical scavenging capacities to 89.71% and 72.39%, respectively. Furthermore, it improved OA transdermal delivery and suppressed UVB-induced HEK cell senescence. In vivo, CA-g-CS-OA-TFs, with their enhanced stability and synergistic antioxidant activity, significantly restored skin barrier function, attenuated collagen and elastic fiber damage, downregulated senescence-associated genes, and relieved oxidative stress in mice with UV-induced photoaging. Collectively, CA-g-CS-OA-TFs represent a promising nanodelivery strategy for superior photoaging protection.