水飞蓟素长循环脂质体制备与抗肿瘤活性研究  

Preparation and Antitumor Activity of Silymarin Long-circulation Liposomes

作　　者：朱钰叶[1] 李晓莉[1] 王伟 孙广明 ZHU Yuye;LI Xiaoli;WANG Wei;SUN Guangming(Xianyang Vocational College, Xianyang 712000, Shaanxi, China)

机构地区：[1]咸阳职业技术学院

出　　处：《辽宁中医药大学学报》2018年第7期65-69,共5页Journal of Liaoning University of Traditional Chinese Medicine

摘　　要：目的：制备水飞蓟素长循环脂质体,并考察其对Hep G2肝癌细胞的抑制率。方法：本研究以水飞蓟素为模型药,采用薄膜分散-挤压法制备了经胆固醇-聚乙二醇2000（Chol-PEG2000）修饰的长循环脂质体,并以外观、粒径、包封率等作为指标考察了氢化大豆磷脂用量、胆固醇用量、药脂比和Chol-PEG2000用量,评价了冻干前后脂质体的粒径、多聚分散系数（Pd I）、Zeta电位、包封率等理化性质;考察了水飞蓟素长循环脂质体在pH 7.4磷酸盐缓冲液（PBS）和大鼠血浆中的释放行为;评价了水飞蓟素长循环脂质体对Hep G2肝癌细胞的体外抗肿瘤细胞活性。结果：最终确定了长循环脂质体的处方组成：氢化大豆磷脂用量为10 mg/m L,胆固醇与氢化大豆磷脂用量比为1∶12.5,药脂比为1∶25,Chol-PEG2000用量为5.0%,所制备的水飞蓟素长循环脂质体的平均粒径为（102.4±39.4）nm,Pd I为0.194,Zeta电位为（-31.6±1.4）m V,包封率为94.7%±2.8%,呈球形或类球形分布,冻干前后粒径、Pd I、Zeta电位和包封率均无显著变化;水飞蓟素长循环脂质体在pH 7.4 PBS中释放缓慢,而在大鼠血浆中释放较快;水飞蓟素长循环脂质体的体外抗肿瘤活性显著高于水飞蓟素溶液（P〈0.05）,说明水飞蓟素长循环脂质体能够有效抑制肝癌细胞的生长与分裂。结论：采用薄膜分散-挤压法制备水飞蓟素长循环脂质体在体外表现出良好的抗肿瘤活性,为水飞蓟素长循环脂质体应用于临床研究奠定实验基础。Objective：To prepare silymarin long-circulation liposomes and investigate its inhibitory effect on Hep G2 liver tumor cells. Methods：Silymarin was used as the model drug. Chol-PEG2000 modified long-circulation liposomes were prepared by membrane dispersion-extrusion method. The physicochemical properties such as particle size distribution,Pd I,Zeta potential and encapsulation efficiency of liposomes were evaluated before and after lyophilization. The drug release behavior of long-circulation liposomes in pH 7.4 phosphate buffer solution and rat plasma was investigated.The in vitro antitumor activity of silymarin long-circulation liposomes on Hep G2 liver tumor cells was evaluated. Results：The formulation of long circulating liposomes was determined. The dosage of hydrogenated soybean phospholipid was 10 mg/m L,the ratio of cholesterol to hydrogenated soybean phospholipid was 1∶12.5,the ratio of drug to lipid was 1∶25,and the dosage of Chol-PEG2000 was 5%. The average diameter of the long-circulation liposomes was（102.4±39.4）nm,the Pd I was 0.194,the Zeta potential was（-31.6±1.4）m V,encapsulation efficiency was 94.7%±2.8%. Silymarin long-circulation liposomes were spherical or spherical-like distribution as seen in transmission electron microscopy. The particle size distribution,Pd I,Zeta potential and encapsulation efficiency did not change significantly before and after lyophilization. Long-circulation liposomes were released slowly in PBS,but released rapidly in rat plasma. Silymarin long-circulation liposomes antitumor activity was significantly higher than the silymarin solutionin vitro（P〈0.05）,indicating that liposomes can effectively inhibit Hep G2 liver cancer cell growth and division. Conclusion：Silymarin long-circulation liposomes prepared by membrane dispersion-extrusion method have good antitumor activity in vitro and lay the experimental foundation for the clinical application.

关 键 词：水飞蓟素 长循环脂质体 薄膜分散-挤压法 抗肿瘤活性 

分 类 号：R284[医药卫生—中药学]