Nitric oxide-releasing nanocarriers integrated with ginsenoside compound K in dissolvable microneedles for androgenetic alopecia

Androgenetic alopecia (AGA) is recognized as a prevalent androgen-mediated disorder characterized by progressive follicular miniaturization and irreversible hair loss, primarily driven by the pathological elevation of dihydrotestosterone (DHT) that disrupts hair follicle microenvironment and induces follicular cells damage. This condition frequently results in profound psychosocial distress and diminished quality of life among affected individuals. In this study, we introduced a novel microneedle-based drug delivery system (CK/GSNO@Lip MN) for the synergistic treatment of AGA. The system was ingeniously engineered for the co-delivery of Ginsenoside Compound K (CK) and S-nitrosoglutathione (GSNO), which possessed distinct hydrophobicities and release kinetics. Specifically, the hydrophobic drug CK activated the PI3K-AKT signaling pathway to upregulate β-catenin expression, while concurrently modulating reactive oxygen species (ROS) levels and alleviating excessive inflammatory responses. Meanwhile, the hydrophilic nitric oxide (NO) donor GSNO released NO to enhance angiogenesis and synergistically regulated inflammatory homeostasis in conjunction with CK, thereby creating a favorable microenvironment for hair regeneration. Ultimately, CK/GSNO@Lip MN achieved significant hair regeneration by modulating the hair follicle microenvironment and promoting the proliferation of follicular cells. This innovative therapeutic strategy provided a comprehensive approach to AGA treatment, with promising potential for broader dermatological applications.