Rosemary oil-based microemulsion co-delivering quercetin and adenosine promotes hair regeneration in androgenetic alopecia via multiple actions

The pathogenesis of androgenetic alopecia (AGA) is driven by heightened androgen receptor signaling, alongside contributing factors of oxidative stress, follicular inflammation, and impaired perifollicular angiogenesis. Existing treatments such as minoxidil and finasteride suffer from limited efficacy, systemic side effects, and high relapse rates. In this study, we developed a rosemary oil (RO)-based microemulsion (QAR ME) for the co-delivery of quercetin (QT) and adenosine (AD) to synergistically target multiple pathological pathways of AGA. Here, RO can not only serve as a component of the oil phase but also function as a functional excipient with inherent antioxidant activity. The optimized QAR ME formulation demonstrated high stability, a small uniform particle size (24.98 ± 0.41 nm). It not only improved the solubility of QT but also enhanced the skin penetration of each active component. In vitro and in vivo evaluations revealed that QAR ME effectively attenuated oxidative stress, suppressed inflammatory responses, promoted angiogenesis, and activated the Wnt/β-catenin pathway, leading to enhanced hair follicle regeneration. It is worth noting that during the 28-day continuous treatment, QAR ME did not show any adverse reactions, which indicates that this therapy has the potential for long-term treatment of AGA. These findings indicate that QAR ME is a promising topical nanotherapy for the safe and effective treatment of AGA.