雷公藤红素脂质体的制备及其对脑胶质瘤U87 MG细胞增殖的抑制作用

Preparation of the celastrol liposome and its anti-proliferative effects on U87 MG glioma cells

建立雷公藤红素的高效液相色谱分析方法,采用薄膜分散法制备雷公藤红素脂质体,并通过正交试验优化处方,对雷公藤红素脂质体的粒径、Zeta电位、形态、体外释放度和体外对脑胶质瘤U87 MG细胞增殖的抑制作用进行考察.结果显示雷公藤红素脂质体的体外分析方法简单可行,制备雷公藤红素脂质体的最佳处方为:药脂质量比1∶40,磷脂与胆固醇质量比6∶1,水化介质为10%(质量分数)海藻糖溶液.按最佳处方制备的脂质体粒径约160 nm,Zeta电位为-35 mV,包封率达到80%以上.所制备的雷公藤红素脂质体呈类球形,在体外释放实验中表现出良好的缓释作用,且其抑制U87 MG细胞增殖的作用强于雷公藤红素溶液,半数抑制浓度(IC50)为7.93μmol/L.综上,制备雷公藤红素脂质体的方法稳定可行,所制备的脂质体理化性质良好并可有效抑制U87 MG细胞增殖.

We established an HPLC method in vitro for celastrol analysis and the celastrol-loaded liposome was prepared using a thin film dispersion method.Orthogonal experiments were conducted to optimize the prescription.Entrapment efficiency,particle size,Zeta potential and the anti-proliferative effects on U87 MG glioma cells of the celastrol-loaded liposome were evaluated.The results showed that the in vitro analysis method for celastrol-loaded liposome was simple and feasible,and the best optimizated prescription was as follows:the mass ratio of drug to lipid was 1∶40,and the mass ratio of phospholipids to cholesterol was 6∶1,with 10%(by mass)trehalose solvent as the hydration medium.For celostrol-loaded liposome prepared by this best prescription,the average particle size was about 160 nm,the Zeta potential was-35 mV and the entrapment efficiency was above 80%.The celastrol-loaded liposome was generally spherical and performed a good preferred release behavior in the in vitro release experiment.Furthermore,the celastrol-loaded liposome had a better anti-proliferative effect on U87 MG cells than celastrol solution,with the IC50 value of 7.93μmol/L.In conclusion,the celastrol-loaded liposome has good physical and chemical properties,and anti-proliferative effect on U87 MG cells.