Magnolol nanomicelles based on valproic acid-modified hyaluronic acid for the treatment of androgenetic alopecia in mice

Magnolol (Mag) exhibits potent antibacterial, anti-inflammatory, and antioxidant effects and is a promising agent for androgenetic alopecia (AGA) treatment, but its poor water solubility limits its clinical application. We thus fabricated modified hyaluronic acid-based follicle-targeted nanomicelles. Hydrophobic valproic acid-modified hyaluronic acid (HA-VPA) was utilized as a nanocarrier for magnolol encapsulation to construct HA-VPA-Mag micelles, followed by systematic characterization of their physicochemical properties. The therapeutic efficacy of HA-VPA-Mag against androgenetic alopecia was assessed in a testosterone propionate-induced AGA mouse model, with a focus on transdermal permeation behavior and hair follicle targeting efficiency. In vitro studies demonstrated sustained magnolol release, enhanced transdermal retention, and selective follicular accumulation. In a testosterone propionate-induced AGA mouse model, enzyme-linked immunosorbent assay (ELISA), Real-time quantitative polymerase chain reaction (RT-qPCR), Western blot (WB), and histopathological analyses revealed that magnolol nanomicelles markedly reversed alopecia symptoms and outperformed free magnolol solution. The hyaluronic acid-valproic acid -based magnolol nanomicelles overcome the drug's poor aqueous solubility, enhance follicular targeting, and significantly improve therapeutic efficacy against AGA. Download: Download high-res image (485KB) Download: Download full-size image