Multistage Transdermal Nitric Oxide Delivery System for the Efficient Treatment of Androgenic Alopecia
Hui Xing, Xinlin Jiang, Ziyi Zhao, Yuhui Yang, Zhen Wang, Yi Yang, Guodong Sun, Shixin Liu, Dong Ma
Abstract
Androgenic alopecia (AGA) is a prevalent progressive hair loss condition. The main therapeutic drug, minoxidil, is limited by its poor efficacy and side effects such as contact dermatitis and hypertrichosis. Nitric oxide (NO), an endothelial-derived relaxing factor, promotes angiogenesis and accelerates blood flow, enhancing nutrient supply similar to minoxidil. Accordingly, we utilized a poly(vinyl alcohol) film (PVA) loaded with hyaluronic acid (HA) liposomes to construct a multistage transdermal NO delivery system (PVA@HL/NONOate) for the treatment of AGA. The HA liposomes provided efficient NO loading and extended release, while the PVA film improved skin penetration and sustained NO release, increasing NO bioavailability. Low-concentration NO effectively enhanced hair follicle vitality and repaired blood vessels. Mechanistically, low-concentration NO could treat AGA mainly by regulating the HIF-1 signaling pathway to promote angiogenesis, reducing inflammation by downregulating the expression of TNFRSF9 and IL-6, repairing hair follicles by downregulating the expression of genes in the CXCL5-IL-17 inflammatory axis.