新型阿霉素隐形阳离子脂质体的制备及体外细胞实验  

Preparation of stealth cationic liposome loaded with doxorubicin and cell studies in vitro

作　　者：吉丽[1] 常爽[1] 何斌[1] 李莉[1] 聂宇[1] 顾忠伟[1] 

机构地区：[1]四川大学国家生物医学材料工程技术研究中心,四川成都610064

出　　处：《华西药学杂志》2012年第1期17-19,共3页West China Journal of Pharmaceutical Sciences

基　　金：教育部博士点基金新教师类项目(批准号:20100181120075);教育部回国基金(批准号:20071108-18-5);教育部重点项目(批准号:109133);四川省科技厅应用基础研究项目(批准号:2008JY0032)

摘　　要：目的制备阿霉素隐形阳离子脂质体(DOX-SCL),并与中性脂质体(DOX-SNL)比较在体外小鼠乳腺癌4T1细胞实验上的差异。方法采用薄膜超声法制备空白脂质体,硫酸铵梯度法包载盐酸阿霉素(DOX);引入赖氨酸-胆固醇酯(Chol-lys)制成阳离子脂质体(CL),同时引入聚乙二醇-胆固醇琥珀酸酯(CHEMS-PEG)制成隐形阳离子脂质体(SCL);采用凝胶柱-UV法测定包封率;采用MTT法测定细胞毒性及体外抗肿瘤活性;通过流式细胞试验考察4T1细胞对脂质体的摄取情况。结果 SCL粒径约为100 nm,Zeta电位约为15.2 mV,对DOX的包封率大于95%;CHEMS-PEG的引入可以有效地降低CL的细胞毒性;与DOX-SNL相比,4T1细胞对DOX-SCL的摄取有所增加,DOX-SCL对4T1细胞的抑制率也更高。结论 SCL作为新型药物载体,可有效地促进DOX在肿瘤细胞中的传递。OBJECTIVE To prepare the stealth cationic liposome（SCL） loaded with doxorubicin（DOX）,and investigate the difference between DOX-SCL and neutral liposome（DOX-SNL） on murine breast carcinoma 4T1 cell line in vitro.METHODS Liposomes loaded with DOX were prepared by film dispersion followed by ammonium sulfate gradient method.Cationic liposome（CL） was formed in the addition of lysine-based cholesterol（Chol-lys）,while SCL was constructed with both Chol-lys and PEGylated cholesterol hemisuccinate（CHEMS-PEG）.The entrapment efficiency was determined by Sephadex G-75-UV.Cytotoxicity and anti-tumor activity in vitro were evaluated by MTT method.Flow cytometry was performed to evaluate the cellular uptake of liposomes by 4T1 cells.RESULTS The results revealed that the mean size of SCL was around 100 nm,with a Zeta potential of 15.2 mV,and the entrapment efficiency was above 95%.The addition of CHEMS-PEG could effectively reduce the cytotoxicity of CL.Compared with DOX-SNL,the uptake of DOX-SCL by 4T1 cells was increased,and DOX-SCL showed higher cell inhibition of 4T1 cells.CONCLUSION SCL could be a promising carrier to deliver encapsulated DOX into tumor cells.

关 键 词：阿霉素 阳离子脂质体 隐形脂质体 细胞毒性 

分 类 号：R94[医药卫生—药剂学]