甲氨喋呤自组装温敏胶束的制备及表征

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

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pH6.8的磷酸盐缓冲液为透析介质,在4℃下每天前12h每隔1h更换透析介质,后12h更换2次,透析3d,所得胶束呈壳核结构的球形,平均粒径为190±15nm,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℃.

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 ℃.