褪黑素隐形脂质体的制备及体外透皮释药性能的研究  

Preparation of stealth liposomes loading melatonin and their in vitro percutaneous permeation

作　　者：张政 闫福鹏 杨程皓 刘晨雨 王友朝 周田田 郝吉福 ZHANG Zheng;YAN Fupeng;YANG Chenghao;LIU Chenyu;WANG Youchao;ZHOU Tiantian;HAO Jifu(School of Pharmaceutical Sciences,Shandong First Medical University&Shandong Academy of Medical Sciences,Taian 271016,China)

机构地区：[1]山东第一医科大学(山东省医学科学院)药学院,山东泰安271016

出　　处：《广东药科大学学报》2022年第1期1-6,共6页Journal of Guangdong Pharmaceutical University

基　　金：2020年山东省级大学生创新创业训练计划项目(S202010439055)。

摘　　要：目的制备褪黑素隐形脂质体并探讨其体外透皮释药性能。方法以褪黑素为模型药物,通过薄膜水化法制备隐形脂质体。采用激光粒度仪测定粒径分布及透射电镜观察外观形貌,超滤离心法测定包封率及载药量,对褪黑素隐形脂质体进行表征,采用Franz扩散池法比较褪黑素隐形脂质体与普通脂质体的体外释药速率。采用扫描电镜(SEM)、差示扫描热分析(DSC)及红外光谱检测经褪黑素隐形脂质体处理后的小鼠皮肤,以探讨其透皮机制。结果褪黑素隐形脂质体的平均粒径为48.87 nm,透射电镜观察所制备的脂质体呈规整的圆球状,无聚集现象;褪黑素隐形脂质体的包封率和载药量分别为73.91%和9.92%。与普通脂质体相比,褪黑素隐形脂质体单位面积累积渗透量和渗透速率分别提高了1.5倍和2倍,显示出较快的渗透性。由SEM可观察到经隐形脂质体处理后,小鼠皮肤表面比较平整光滑,角质层细胞水化程度较高,细胞间隙明显增加;DSC及红外结果可知,角蛋白的结构发生变化,脂质峰发生红移。结论将褪黑素制备成隐形脂质体可以提高其透皮效果,为褪黑素的进一步开发和利用提供了依据。Objective To prepare stealth liposomes loading melatonin and evaluate their in vitro percutaneous permeation properties.Methods Melatonin-stealth liposomes were prepared by film hydration method.The physicochemical properties were characterized after determination of particle size distribution,observation of the morphology with transmission electron microscope(TEM)and measurement of the entrapment efficiency and drug loading by ultrafiltration centrifugation method.The in vitro percutaneous permeation rate of melatonin stealth liposomes and melatonin-liposomes was determined by Franz diffusion cell.The mice skin structure treated with melatonin stealth liposomes was detected by scanning electron microscope(SEM),differential scanning thermal analysis(DSC)and Fourier transform infrared spectroscopy(FTIR)to explore the potential transdermal mechanism.Results The average particle size of melatonin-stealth liposomes was 48.87 nm.The morphology of melatonin-stealth liposomes was regular and spherical without aggregation.The entrapment efficiency and drug loading of melatonin stealth liposomes were 73.91%and 9.92%,respectively.Compared with melatonin liposomes,the cumulative penetration and penetration rate per unit area of melatonin-stealth liposomes were increased by 1.5 times and 2 times,respectively,which showed a relative faster permeability.It could be also observed by SEM that after treatment with the stealth liposomes,the skin was relatively flat and smooth and had the high hydration degree of stratum corneum as well as the increased dintercellular space.DSC and IR results showed that the structure of keratin changed and the lipid peak of stratum corneum shifted red.Conclusion The preparation of melatonin into stealth liposomes can improve the transdermal effect,which lays a foundation for the further development and utilization of melatonin.

关 键 词：褪黑素 隐形脂质体 体外透皮试验 透皮机制 

分 类 号：R944.9[医药卫生—药剂学]