聚乙二醇包裹表阿霉素脂质体的制备及评价

doi:10.3969/j.issn.1006-7795.2015.02.003

首都医科大学学报 ›› 2015, Vol. 36 ›› Issue (2): 166-172.doi: 10.3969/j.issn.1006-7795.2015.02.003

聚乙二醇包裹表阿霉素脂质体的制备及评价

黄萍¹, 崔纯莹¹, 王玉记², 吴建辉²

1. 首都医科大学化学生物学与药学院药剂学系, 北京 100069;
2. 首都医科大学化学生物学与药学院药物化学系, 北京 100069

收稿日期:2014-12-08 出版日期:2015-04-21 发布日期:2015-04-16
通讯作者: 吴建辉 E-mail:wujianhui01@126.com
基金资助:
"十二五"重大新药创制科技重大专项(2011ZX09302-007-01)。

Preparation and evaluation of a liposome of PEG and epirubicin

Huang Ping¹, Cui Chunying¹, Wang Yuji², Wu Jianhui²

1. Department of Pharmacy, School of Chemical Biology and Pharmaceutical Sciences, Capital Medical University, Beijing 100069, China;
2. Department of Medicinal Chemistry, School of Chemical Biology and Pharmaceutical Sciences, Capital Medical University, Beijing 100069, China

Received:2014-12-08 Online:2015-04-21 Published:2015-04-16
Supported by:
This study was supported by Significant New Drugs Creation "Five-Year" Plan Special Science and Technology Major(2011ZX09302-007-01).

摘要/Abstract

摘要： 目的制备聚乙二醇(polyethylene glycol,PEG)包裹表阿霉素脂质体,对其药剂学性质和活性进行评价。方法采用乳化溶剂挥发法制备聚乙二醇包裹表阿霉素的脂质体,用扫描电镜和透射电镜观察其形态,用激光纳米粒度仪测定粒径分布及Zeta电位、并对包封率、稳定性及体外释药特性进行研究,采用MMT法和S180小鼠模型评价体内外抗肿瘤活性。结果聚乙二醇包裹表阿霉素的脂质体的粒径为(231.4±2.0)nm,动电位为(-25.62±0.68)mV,包封率为(53.14±4.85)%,各项稳定性均有明显提高,体外释放缓慢,小鼠剂量可增加到6 μmol/kg,给药间隔可延长至72 h,并显示比表阿霉素好的抗肿瘤活性。结论本实验获得了较理想的聚乙二醇包裹表阿霉素脂质体,体外释药符合长效制剂特征,血浆中稳定,具有pH敏感性,可改善表阿霉素用药安全性,延长药物作用时间。

关键词: 聚乙二醇, 左旋聚乳酸, 表阿霉素, 脂质体, 长效循环

Abstract: Objective To prepare a novel lipsome of polyethylene glycol packaged with epirubicin(EPI) liposomes, to explore the properties of the liposome and evaluate its antitumor activities. Methods Emulsion solvent evaporation method was used to prepare the liposome. The morphology of the liposome was observed by transmission electron microscope(TEM) and scanning electron microscope(SEM). The characteristics such as particle size, zeta potential, drug entrapment rate, stability and releasing property in vitro were studied. The anti-proliferation activities of EPI liposome and EPI against cancer cells were evaluated by MTT assay. The antitumor activity in vivo was assayed on S180 mouse model. Results The average particle size and the zeta potential of the liposome were (231.4±2.0) nm and (-20~30) mV, respectively, and the average entrapment efficiency was (53.14±4.85)%. This novel liposome improved the stability, slowed the releasing rate, enhanced the activity, increased the tolerance and extended dosing interval. Conclusion PEG and EPI formed a novel liposome capable of long-acting, plasma-stabile, pH-dependent release, and highly inhibitory effect against tumor growth.

Key words: polyethylene glycol(PEG), levo-poly lactic acid(PLLA), epirubicin, liposome, long-acting

中图分类号:

R965.1

黄萍, 崔纯莹, 王玉记, 吴建辉. 聚乙二醇包裹表阿霉素脂质体的制备及评价[J]. 首都医科大学学报, 2015, 36(2): 166-172.

Huang Ping, Cui Chunying, Wang Yuji, Wu Jianhui. Preparation and evaluation of a liposome of PEG and epirubicin[J]. Journal of Capital Medical University, 2015, 36(2): 166-172.

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聚乙二醇包裹表阿霉素脂质体的制备及评价

Preparation and evaluation of a liposome of PEG and epirubicin

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