Rao Yuefeng, Zheng Feiyue, Liang Xingguang, Wang Huiyuan, Zhang Jin, Lu Xiaoyang
a The First Affiliated Hospital, College of Medicine , Zhejiang University , China .
b College of Pharmaceutical Sciences , Zhejiang University , China .
Drug Deliv. 2015 Dec;22(8):1003-1009. doi: 10.3109/10717544.2013.839128. Epub 2013 Oct 4.
The skin accumulation of therapeutic agents affects the efficiency of topical drug delivery. In this study, in vitro distribution of finasteride of ethosomes and liposomes in human cadaver skin after percutaneous delivery were investigated. Experiments were performed using modified Franz diffusion cells. Finasteride ethosomes, liposomes or hydroethanolic solutions were used as donor medium. Drug distribution at different skin layers and depths were studied by hotplate separation and frozen horizontal slicing technique. The result showed that the accumulation of finasteride in skin ranged from 9.7-24.3 μg/cm at 12 or 24 hours. The ethosomes demonstrated better enhancing ability to deliver finasteride into the dermis layer than liposomes did. The finasteride concentration in the dermis layer from ethosomes was more than sevenfold higher than from liposomes. The finasteride accumulation in ethosomes group showed a distinctive reversed distribution profile. This distinctive reversed distribution profile is meaningful for exerting a favorable pharmacological effect for finasteride. The drug distribution profile in skin layers showed no significant difference between 12 and 24 hours application (p > 0.05). The study demonstrated that finasteride can be accumulated at target site more effectively and maintained at higher level through the application of novel ethosomal carriers.
治疗剂在皮肤中的蓄积会影响局部给药的效率。在本研究中,对非那雄胺乙醇脂质体和脂质体经皮给药后在人体尸体皮肤中的体外分布进行了研究。实验使用改良的Franz扩散池进行。非那雄胺乙醇脂质体、脂质体或氢乙醇溶液用作供体介质。通过热板分离和冷冻水平切片技术研究了不同皮肤层和深度的药物分布。结果表明,12或24小时时,非那雄胺在皮肤中的蓄积量为9.7-24.3μg/cm。乙醇脂质体将非那雄胺输送到真皮层的增强能力比脂质体更好。乙醇脂质体组真皮层中的非那雄胺浓度比脂质体组高七倍多。乙醇脂质体组中非那雄胺的蓄积呈现出独特的反向分布特征。这种独特的反向分布特征对于非那雄胺发挥良好的药理作用具有重要意义。在12小时和24小时给药时,皮肤层中的药物分布特征无显著差异(p>0.05)。该研究表明,通过应用新型乙醇脂质体载体,非那雄胺可以更有效地在靶部位蓄积并维持在较高水平。