Shan Yujun, Xu Chang, Guo Yanxia, Wen Le, Zhou Shanshan, Fang Li, Xu Junjun, Zheng Hangsheng
School of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Hangzhou 311402, China.
The First People's Hospital of Yuhang District, Hangzhou 311100, China.
Int J Pharm. 2025 May 30;677:125642. doi: 10.1016/j.ijpharm.2025.125642. Epub 2025 Apr 24.
Androgenic alopecia (AGA) represents one of the most prevalent forms of hair loss. Liposomes (LPSs), acting as a localized dermal drug reservoir with sustained release property, can effectively prolong and enhance drug retention within the skin. Minoxidil sulfate (MXS), a potent active metabolite of minoxidil (MX) for promoting hair growth, exhibits instability in aqueous solution and faces difficulties in depositing within the deep dermal hair follicle regions. In this study, MXS-LPSs were fabricated via the thin-film hydration-dispersion method combined with an ammonium sulfate gradient active drug loading process, and their physicochemical characteristics were comprehensively characterized. The skin permeation/deposition properties of the drug from the MXS-LPSs were investigated by Franz diffusion cell method on ex vivo rat skin, and the mechanism underlying the targeted drug delivery of LPSs to hair follicles was explored by confocal laser scanning microscopy (CLSM). The pharmacodynamic evaluation of MXS-LPSs was carried out in AGA model rats. The optimized MXS-LPSs were uniformly dispersed with enhanced stability. The average vesicle size of MXS-LPSs was 129.46 ± 7.04 nm, the zeta potential was -25.57 ± 4.79 mV, the encapsulation efficiency (EE) was 92.72 ± 0.75 %, and the drug loading (DL) was 2.80 ± 0.12 %. The results of ex vivo skin permeation/deposition showed that the cumulative permeated drug amount (Q) from MXS-LPS, MX tincture and MXS solution at 36 h was 225.98 ± 11.53, 19.79 ± 1.97 and 584.42 ± 2.33 μg·cm, respectively. The deposited drug amount in the skin beneath the stratum corneum from MXS-LPSs, MX tincture and MXS solution accounted for about 59.80 ± 26.27 %, 43.18 ± 6.58 % and 32.55 ± 1.61 % of that in the whole skin, respectively. It is remarkable that MXS-LPSs showed a considerably increased accumulation in hair follicles when compared to MXS solution. The results of pharmacodynamic tests demonstrated that, compared to MX tincture, MXS-LPSs could more effectively stimulate hair regrowth and avoided the adverse effects. Importantly, the MXS-LPSs also reduced skin irritation and sensitization. Consequently, MXS-LPSs hold substantial promise in the treatment of AGA.
雄激素性脱发（AGA）是最常见的脱发形式之一。脂质体（LPSs）作为具有缓释特性的局部皮肤药物储库，可有效延长并增强药物在皮肤内的滞留。硫酸米诺地尔（MXS）是米诺地尔（MX）促进头发生长的一种强效活性代谢物，在水溶液中不稳定，且难以沉积到真皮深层毛囊区域。在本研究中，通过薄膜水化分散法结合硫酸铵梯度主动载药工艺制备了MXS-LPSs，并对其理化特性进行了全面表征。采用Franz扩散池法在离体大鼠皮肤上研究了药物从MXS-LPSs中的皮肤渗透/沉积特性，并用共聚焦激光扫描显微镜（CLSM）探索了LPSs靶向毛囊给药的机制。在AGA模型大鼠中对MXS-LPSs进行了药效学评价。优化后的MXS-LPSs均匀分散且稳定性增强。MXS-LPSs的平均囊泡大小为129.46±7.04nm，ζ电位为-25.57±4.79mV，包封率（EE）为92.72±0.75%，载药量（DL）为2.80±0.12%。离体皮肤渗透/沉积结果表明，36h时MXS-LPSs、MX酊剂和MXS溶液的累积渗透药量（Q）分别为225.98±11.53、19.79±1.97和584.42±2.33μg·cm²。MXS-LPSs、MX酊剂和MXS溶液在角质层下皮肤中的沉积药量分别占全皮沉积药量的59.80±26.27%、43.18±6.58%和32.55±1.61%。值得注意的是，与MXS溶液相比，MXS-LPSs在毛囊中的蓄积显著增加。药效学试验结果表明，与MX酊剂相比，MXS-LPSs能更有效地刺激头发生长并避免不良反应。重要的是，MXS-LPSs还降低了皮肤刺激性和致敏性。因此，MXS-LPSs在AGA治疗中具有很大的前景。
