Plant Nanovesicles Integrate Bioactivity and Transdermal Finasteride Delivery for Androgenetic Alopecia

Androgenetic alopecia (AGA) is a progressive hair loss disorder with limited effective therapeutic options. Although finasteride (FIN) remains a first-line treatment, its oral administration is frequently associated with systemic side effects. To overcome this limitation, we developed biomimetic Platycladi cacumen-derived nanovesicles (PcNs)─a traditional medicinal herb known for its hair-growth-promoting properties─as multifunctional carriers for transdermal FIN delivery. PcNs significantly enhanced skin permeation and local drug retention, promoting drug accumulation within the epidermal and dermal layers, while concurrently reducing oxidative stress. In a testosterone-induced AGA mouse model, topical application of FIN-loaded PcNs (FIN-PcNs) effectively reversed hair follicle miniaturization and robustly stimulated hair regeneration. Compared to minoxidil, FIN-PcNs exhibited superior therapeutic efficacy in promoting hair regrowth. Mechanistically, PcNs alleviated hair loss by scavenging reactive oxygen species, modulating inflammatory signaling pathways, and upregulating key genes associated with hair follicle regeneration. Collectively, this study presents a plant-derived nanovesicle-based transdermal platform that integrates intrinsic bioactivity with local drug delivery, offering a safe and effective strategy for AGA treatment and underscoring the broader potential of plant-derived nanocarriers in precision dermatology.