甘草次酸修饰的人参皂苷Rh_2脂质体的制备及其体外评价  

Preparation and in vitro Evaluation of Ginsenoside Rh_2 Liposomes Surface-modified with Glycyrrhetinic Acid

作　　者：王琳[1] 杨智钧[2] 向敏[1] 吴纪凯[1] 方晨[2] 

机构地区：[1]苏州卫生职业技术学院,江苏苏州215009 [2]香港浸会大学中医药学院,香港999077

出　　处：《中国实验方剂学杂志》2015年第5期29-32,共4页Chinese Journal of Experimental Traditional Medical Formulae

基　　金：江苏省优秀骨干教师境外研修项目

摘　　要：目的:制备由甘草次酸修饰的人参皂苷Rh2脂质体,评价其体外理化性质和对人肝癌细胞SMMC-7721的生长抑制作用。方法:采用薄膜分散法制备普通的人参皂苷Rh2脂质体(Rh2-L)和甘草次酸修饰的人参皂苷Rh2脂质体(GA-Rh2-L),利用UPLC测定人参皂苷Rh2的含量,流动相乙腈-水(28∶72),流速0.3 m L·min-1,检测波长203 nm。考察脂质体的包封率、粒径、体外释放率及Zeta电位,运用噻唑蓝(MTT)法评价人参皂苷Rh2溶液,Rh2-L和GA-Rh2-L对SMMC-7721细胞体外增殖的抑制作用。结果:与Rh2-L相比,GA-Rh2-L的包封率、粒径、体外释放率及Zeta电位等理化性质均无显著性差异。Rh2-L和GARh2-L的包封率分别为(91.67±1.05)%,(95.54±2.23)%,粒径(138.6±45.8),(146.5±48.9)nm,Zeta电位-(12.75±0.34),-(14.79±0.67)m V,72 h的体外释放率(84.67±7.23)%,(89.03±8.61)%。人参皂苷Rh2溶液在12 h内释药率达(91.23±5.17)%。细胞用药2 d后,GA-Rh2-L对SMMC-7721的半抑制率(IC50)分别为人参皂苷Rh2和Rh2-L的0.524,0.596倍,并呈浓度和时间以依赖关系。结论:甘草次酸修饰不会影响人参皂苷Rh2脂质体得理化性质,还可增加其对细胞的靶向性,增加了细胞毒性,为肝肿瘤的靶向治疗提供了新思路。Objective： To encapsulate ginsenoside Rh2 within glycyrrhetinic acid modified liposomes and investigate its physicochemical properties and in vitro inhibitory effect on SMMC-7721 ceils. Method： Ginsenoside Rh2 liposomes （Rh2-L） and ginsenoside Rh2 liposomes surface-modified with glycyrrhetinic acid （GA-Rh2-L） were prepared by film dispersion method, UPLC was employed to determine the content of ginsenoside Rh2 with mobile phase of acetonitrile-water （28 ： 72） , flow rate of 0.3 mL·min^-1 and detection wavelength at 203 nm. Encapsulation efficiency （EE） , particle size, Zeta potential and in vitro release were measured, MTT experiment was adopted to evaluate inhibitory effect of ginsenoside Rh2 solution, Rh2-L and GA-Rh2-L on SMMC-7721 cells. Result： Modification of glycyrrhetinic acid showed no effect on physicochemical properties of Rh2-L, such as EE, particle size, Zeta potential and in vitro release. EE of Rh2-L and GA-Rh2-L were （91.67 ± 1.05） % and （95.54± 2. 23） %, average particle size of them were （ 138.6 ± 45.8） nm and （ 146.5±48.9） nm, Zeta potential of them were - （12.75 ±0.34） mV and - （14. 79 ±0. 67） mV, respectively. In vitro release of ginsenoside Rh2 from Rh2-L and GA-Rh2-L within 72 h were （84. 67±7.23）% and （89.03 ±8.61 ）% , while ginsenoside Rh2 solution released （91.23 ± 5.17）% within 12 h. In vitro cytotoxicities （IC50） of GA-Rh2-L on SMMC-7721 cells was increased by 0. 524 fold compared with ginsenoside Rh2 solution and 0. 596 fold compared with Rh2-L. Ginsenoside Rh2 solution, Rh2-L and GA-Rh2-L all inhibited proliferation of SMMC-7721 cells in dose-and-time-dependentmanners. Conclusion： Glycyrrhetinic acid modification can not affect physicochemical properties of Rh2-L, and it can increase targeting efficiency of liposomes on hepatocellular carcinoma, thus resulting in higher cytotoxicities in comparison with Rh2-L. This study provides new ideas for targeted-therapy to hepatocellular carcinoma.

关 键 词：甘草次酸 人参皂苷RH2 脂质体 肝肿瘤 薄膜分散法 

分 类 号：R283.6[医药卫生—中药学] R944.9[医药卫生—中医学]