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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℃.
Methotrexate temperature-sensitive micelles were prepared by dialysis using poly (isopropylacrylamideacrylamide) poly (n-butylmethacrylate) block copolymer. The frequency of membrane permeation, the frequency of dialysis medium replacement, Dialysis time and water pretreatment on the particle size distribution of micelles and drug / copolymer feed mass ratio, dialysis temperature and dialysis medium on the drug entrapment efficiency, the determination of the micelles minimum critical solution temperature, particle size Distribution and micelle morphology.The results show that the optimal conditions for the preparation of micelles are as follows: drug / block copolymer mass ratio 1:10, pH6.8 phosphate buffer as dialysis medium, at 4 ℃ The dialysis medium was changed every other hour for 12 hours before dialysis twice a day, after dialysis for 12 hours and dialysis for 3 days. The obtained micelles were spherical in shape with a putamen structure, the average particle diameter was 190 ± 15 nm, the polydispersity index was 0.16 and the entrapment efficiency was 15% , Micelles the lowest critical solution temperature is 41 ℃.