Hydrogel Microneedles Loaded With a Reactive Oxygen Species (ROS)-Responsive Carbon Monoxide Donor and Finasteride for Synergistic Treatment of Androgenetic Alopecia

Androgenetic alopecia (AGA) is highly prevalent, yet its treatment is limited by systemic side effects and poor patient compliance. This study aims to develop a topical delivery system for synergistic, effective, safe, and highly compliant AGA treatment. A methacrylated hyaluronic acid (HAMA)-based hydrogel microneedle patch (C-F-HMN) co-loaded with a carbon monoxide-releasing molecule (CORM-401) and finasteride (FIN) was prepared. CORM-401 and FIN were formulated into CORM-401@Pluronic F127 (CO@F127) micelles and FIN@hydroxypropyl-β-cyclodextrin (HP-β-CD) inclusion complexes, respectively. Efficacy, mechanisms, and biocompatibility were evaluated in a testosterone-induced AGA mouse model. C-F-HMN achieved efficient local drug delivery, minimized systemic exposure, and sustained efficacy. FIN reduced dihydrotestosterone (DHT) production by inhibiting 5α-reductase; CORM-401 consumed scalp reactive oxygen species (ROS) and released carbon monoxide (CO) to improve the hair follicle microenvironment. Compared with monotherapy and minoxidil, C-F-HMN showed superior hair regrowth, activated the Wnt/β-catenin pathway, inhibited the transforming growth factor-β (TGF-β)/bone morphogenetic protein (BMP) pathway, and exhibited good biocompatibility without systemic toxicity. This study establishes a novel, effective, safe, and highly patient-compliant topical combination therapy for AGA, overcoming the limitations of traditional treatments and providing a new strategy for clinical AGA management.