Advanced hyaluronic acid-modified niosomes for percutaneous delivery of resveratrol in the treatment of aged skin

A niosome-based delivery system incorporating hyaluronic acid-modified Poloxamer 407 (P407-LHA) was developed to enhance the topical delivery of resveratrol (RSV). It was proposed that the system targets CD44 receptors on human fibroblast cells to improve skin penetration, drug accumulation, and anti-aging efficacy. In this study, the niosome formulations composed of non-ionic P407, P407-LHA, and their blends (P407/P407-LHA(2/1) and P407/P407-LHA(1/2)) were investigated. The grafting ratio of LHA on P407-LHA was 32.93 ± 0.73 %. RSV-loaded niosomes (RSV@niosomes) exhibited particle sizes ranging from 200 to 300 nm and a negative zeta potential, and the LHA-modified niosomes enhanced the RSV payload. In vitro skin penetration demonstrated that RSV@P407/P407-LHA(1/2) niosomes achieved the highest RSV accumulation in both the epidermis and dermis compared to the other formulations. Additionally, RSV@P407/P407-LHA(1/2) niosomes induced the highest collagen production in H2O2-stimulated L929 cells (142.64 ± 7.44 %) compared to untreated cells (66.94 ± 0.38 %). In aged Wistar rat skin, drug deposition in the epidermis and dermis followed the order: RSV@P407/P407-LHA(1/2) niosomes > RSV@P407 niosomes > RSV solution. The RSV@P407/P407-LHA(1/2) niosomes not only efficiently inhibited ROS generation (41.27 ± 5.25 % relative to the control) but also promoted collagen production, increasing from 65.93 ± 2.88 % to 172.95 ± 2.79 %. These results elucidate that the combination of resveratrol and LHA-based niosomes effectively enhances anti-aging efficacy through improved skin penetration and drug accumulation.