Multistage\nTransdermal Nitric Oxide Delivery System\nfor the Efficient Treatment of Androgenic Alopecia

Androgenic\nalopecia (AGA) is a prevalent progressive hair loss\ncondition. The main therapeutic drug, minoxidil, is limited by its\npoor efficacy and side effects such as contact dermatitis and hypertrichosis.\nNitric oxide (NO), an endothelial-derived relaxing factor, promotes\nangiogenesis and accelerates blood flow, enhancing nutrient supply\nsimilar to minoxidil. Accordingly, we utilized a poly(vinyl alcohol)\nfilm (PVA) loaded with hyaluronic acid (HA) liposomes to construct\na multistage transdermal NO delivery system (PVA@HL/NONOate) for the\ntreatment of AGA. The HA liposomes provided efficient NO loading and\nextended release, while the PVA film improved skin penetration and\nsustained NO release, increasing NO bioavailability. Low-concentration\nNO effectively enhanced hair follicle vitality and repaired blood\nvessels. Mechanistically, low-concentration NO could treat AGA mainly\nby regulating the HIF-1 signaling pathway to promote angiogenesis,\nreducing inflammation by downregulating the expression of TNFRSF9\nand IL-6, repairing hair follicles by downregulating the expression\nof genes in the CXCL5-IL-17 inflammatory axis.