Controlled Release of Minoxidil through Hydrogel Cross-Linking to Treat Androgenetic Alopecia

Minoxidil is the only FDA approved topical treatment for androgenetic alopecia, which is male- or female-pattern hair loss. However, its use is limited by its efficacy and tolerability. Here, we describe a novel bioengineered approach to improve local delivery to the skin. We showed that Schiff bases form between the diamines of minoxidil and aldehyde-modified hyaluronic acid, leading to cross-linking and formation of injectable hydrogels. Hydrogels exhibited tunable release of minoxidil over 6 weeks <i>in vitro</i> with induction of hair growth <i>in vivo</i> in a mouse model after intradermal injection. To improve delivery, hydrogels were fabricated into hydrogel-forming microneedle patches, which allowed controlled, precise, and uniform delivery of minoxidil into skin. Through our approach, we formed highly mechanically robust microneedle patches with heights of 600 or 800 μm with sufficient mechanical strength to penetrate human skin. Minoxidil hydrogel microneedle patches similarly led to anagen induction in a mouse model. Our technology represents a promising new approach to improve minoxidil use and patient outcomes in androgenetic alopecia.