Nitric Oxide Donor and Minoxidil Co‐Loaded Microneedles Improving Hair Loss Treatment

ABSTRACT The local application of minoxidil tincture has been widely used clinically for the treatment of androgenetic alopecia (AGA). However, there are significant limitations, including ineffectiveness on its own, poor patient compliance, and low transdermal absorption. Microneedles (MNs) can puncture the stratum corneum painlessly and increase drug absorption through the skin. Additionally, nitric oxide (NO) has been shown to improve blood supply to hair follicles and reduce inflammation. Therefore, we prepared a kind of hair‐growth‐promoting MNs that can co‐deliver minoxidil and NO donor for AGA treatment. In simple terms, nanogels (MHMA) were formed through the photopolymerization of methacrylate hyaluronic acid (MeHA) and methacrylate arginine (MeArg) as an NO donor. Through optimized formulation design, minoxidil was efficiently encapsulated within the MHMA nanogels with a particle size of 522.9 nm, which facilitates targeting of hair follicles. Subsequently, the MNs were prepared using a micro‐molding method. Both in vitro and in vivo experiments demonstrated that the hair‐growth‐promoting MNs could efficiently deliver minoxidil and NO donor by just 3 min pressing on the mouse skin. It effectively promoted the transition of hair follicles to the growth phase and stimulated angiogenesis around the follicles, ultimately leading to hair regeneration in the alopecia mouse model. Overall, the proposed hair growth hair‐growth‐promoting MNs can efficiently and painlessly deliver minoxidil and NO donor into the skin, thus offering a promising new direction for clinical AGA treatment.