Optimizing efficacy: Hyaluronic acid liposomes encapsulating minoxidil for enhanced transdermal delivery and treatment of androgenetic alopecia

Minoxidil (Mi) is currently one of the most commonly used drugs for the treatment of hair loss in clinical settings. It works by accelerating blood flow around the hair follicles, enhancing local oxygen and nutrient supply, thereby promoting hair growth. However, traditional formulations of Mi have a short residence time on the skin, are prone to causing allergic reactions, scaling, and may even induce systemic hypertrichosis as side effects. This highlights the urgent need for the development of more efficient and safer delivery systems to improve its therapeutic efficacy. In previous studies, our team developed a high molecular weight hyaluronic acid-based delivery platform (HL) with excellent skin penetration, anti-inflammatory properties, and tissue repair capabilities. In this study, we used the HL delivery material as a carrier for Mi and developed a Mi delivery system with high drug encapsulation efficiency and good biological safety—HL@Mi. This delivery system encapsulates Mi within HL using techniques such as reverse evaporation, high-speed homogenization, and microjet high-pressure methods. Fluorescent labeling and high-performance liquid chromatography (HPLC) were employed to confirm that HL@Mi significantly enhanced the skin penetration and retention of Mi, effectively improving the local bioavailability of Mi. In vitro experiments, HL@Mi significantly reduced the cytotoxicity of Mi, while optimizing the hair follicle microenvironment by promoting angiogenesis and regulating the expression of IL-6, MMP3, and β-catenin genes associated with hair follicle function. In an established androgenetic alopecia animal model, HL@Mi significantly downregulated the expression of inflammatory factors such as IL-6, TNF-α, and TGF-β1 in the skin, while upregulating Ki67 expression in the hair follicle tissue, thereby accelerating hair growth and effectively improving hair loss symptoms. Moreover, HL@Mi exhibited good biocompatibility and safety. In summary, HL@Mi, as a novel transdermal delivery system, not only provides a more efficient and safer clinical alternative for Mi in the treatment of androgenetic alopecia, but also offers valuable technical insights for other local drug delivery strategies.