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›› 2013, Vol. 13 ›› Issue (3): 474-480.

• 生化工程专栏 • 上一篇    下一篇

甲氨喋呤自组装温敏胶束的制备及表征

孙飞龙 王玉霞 程刚 韦祎 马光辉   

  1. 沈阳药科大学药学院 中国科学院过程工程研究所生化工程国家重点实验室 沈阳药科大学药学院 中国科学院过程工程研究所生化工程国家重点实验室 中国科学院过程工程研究所生化工程国家重点实验室
  • 收稿日期:2013-04-19 修回日期:2013-05-08 出版日期:2013-06-20 发布日期:2013-06-20
  • 通讯作者: 孙飞龙

Preparation and Characterization of Self-assembled Thermo-sensitive Micelles Encapsulated with Methotrexate

SUN Fei-long WANG Yu-xia CHENG Gang WEI Yi MA Guang-hui   

  1. College of Pharmaceutical Sciences, Shenyang Pharmaceutical Universit State Key Lab of Biochemical Engineering, Institute of Process Engineering, CAS College of Pharmaceutical Sciences, Shenyang Pharmaceutical Universit State Key Lab of Biochemical Engineering, Institute of Process Engineering, CAS State Key Lab. Biochem. Eng., Inst. Process Eng., Chinese Academy of Sciences
  • Received:2013-04-19 Revised:2013-05-08 Online:2013-06-20 Published:2013-06-20
  • Contact: SUN Fei-long

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摘要： 利用聚(异丙基丙烯酰胺-丙烯酰胺)-聚(甲基丙烯酸正丁酯)嵌段共聚物，以透析法制备甲氨喋呤温度敏感型胶束，考察了过膜次数、透析介质更换频率、透析时间和预加入水分等对胶束粒径分布的影响及药物/共聚物投料质量比、透析温度和透析介质对药物包封率的影响，测定了胶束的最低临界溶解温度，对粒径分布和胶束形态进行了表征. 结果表明，制备胶束的优化条件为：药物/嵌段共聚物投料质量比1:10，以pH 6.8的磷酸盐缓冲液为透析介质，在4℃下每天前12 h每隔1 h更换透析介质，后12 h更换2次，透析3 d，所得胶束呈壳-核结构的球形，平均粒径为190±15 nm，多分散指数为0.16，药物包封率为15%，胶束最低临界溶解温度为41℃.

关键词: 两亲性嵌段共聚物, 自组装, 温敏胶束, 水不溶性, 甲氨喋呤

Abstract: Thermo-sensitive micelles encapsulated with methotrexate (MTX) were prepared using poly(isopropylacrylamide- co-acrylamide)-b-poly(n-butyl meth acrylate) block copolymers by dialysis method. The effects of trans-membrane times, frequency of replacing dialysis medium, dialysis duration and pre-added water content on their size distribution, and the effects of mass ratio of MTX to block copolymer, temperature and dialysis medium on their encapsulation efficiency were investigated. The lower critical solution temperature (LCST) of micelles was determined. Their size distribution and shape were observed. The results showed that under the optimized conditions of mass ratio of drug/block copolymer 1:10, dialysis medium pH 6.8 phosphate buffer solution, and frequency of replacing dialysis medium each 1 h for the first 12 h, twice for the later 12 h each day at 4℃ for 3 d, the average size of micelles was 190±15 nm with polydispersity index 0.16, and drug encapsulation efficiency 15.0%. The final micelles were spherical with a core-shell structure and their LCST was around 41℃.

Key words: amphiphilic block copolymer, self-assembling, thermo-sensitive micelles, water-insolubility, methotrexate

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