Microneedle-Based Codelivery of Platycladus orientalis-Derived Extracellular Vesicles and Minoxidil Nanoparticles for Androgenetic Alopecia Treatment.

Androgenetic alopecia (AGA) is a common hair disorder in which limited follicular drug delivery and an inflammatory and oxidative follicular microenvironment reduce topical efficacy. Herein, we developed a fast-dissolving microneedle (MN) patch of chondroitin sulfate and carboxymethyl chitosan for localized codelivery of Platycladus orientalis leaf-derived extracellular vesicles (PO-EVs) and minoxidil nanoparticles (MXD NPs). PO-EVs were separated and characterized as nanoscale vesicles and were shown to possess antioxidant, anti-inflammatory, and pro-angiogenic activities relevant to hair follicle maintenance. MXD NPs were prepared by thin-film hydration to improve the minoxidil solubility and local retention. Both were loaded into microneedles with sufficient mechanical strength that could dissolve rapidly in the skin. In a mouse model of androgenic alopecia, repeated dual-loaded MN treatment accelerated the telogen-to-anagen transition, increased hair-covered area and shaft thickness, and restored follicular morphology. Mechanistic studies showed that hair follicle stem cells were activated and proliferated, perifollicular oxidative stress and inflammation were reduced, and microvessel density around hair follicles was increased. No evident skin irritation or systemic toxicity was observed. This MN codelivery strategy improves hair regrowth by combining efficient minoxidil delivery with PO-EV-mediated microenvironment restoration and may be extended to other inflammatory/oxidative skin disorders impairing regeneration.