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目的:制备叶酸介导的普兰多糖-阿霉素聚合物前药(FA-MP-DOX),实现阿霉素药物的靶向控制释放。方法:将普鲁兰多糖用马来酸酐进行修饰后,通过酰胺键键合阿霉素制备得到普鲁兰多糖-阿霉素(MP-DOX),继而酯键键合叶酸制备得到叶酸介导的普鲁兰多糖-阿霉素聚合物前药(FA-MP-DOX)。红外光谱、核磁共振光谱表征聚合物药物的结构,动态透析法模拟体外释药特性,监测不同pH值聚合物药物中阿霉素的释药特性,同时采用人口腔表皮样癌细胞(KB细胞)测定聚合物药物体系的细胞毒性。结果:①经核磁共振表征FA-MP-DOX聚合物合成完成。②在pH2.5、pH5.0及pH7.4的PBS缓冲体系16h中,阿霉素药物累积释放率分别为49.1%,30.3%和15.3%,证实FA-MP-DOX中阿霉素的释放具有pH依赖性。③细胞实验证实FA-MP-DOX的细胞毒性高于阿霉素和MP-DOX。结论:FA-MP-DOX聚合物药物有望成为阿霉素智能型控释和靶向性药物载体。
OBJECTIVE: To prepare folic acid-mediated pullulan-doxorubicin prodrug (FA-MP-DOX) for the targeted controlled release of doxorubicin. Methods: Pullulan polysaccharide was modified with maleic anhydride, then the doxorubicin was prepared through amide bond, and then pullulan-doxorubicin (MP-DOX) was prepared. Then folate-mediated Of pullulan-doxorubicin polymer prodrug (FA-MP-DOX). Infrared spectroscopy and nuclear magnetic resonance spectroscopy were used to characterize the structure of polymer drugs. Dynamic dialysis was used to simulate drug release characteristics in vitro. The release characteristics of doxorubicin in polymer drugs with different pH values were monitored. Human oral epidermoid carcinoma cells (KB cells) The cytotoxicity of the polymer drug system was determined. Results: ① The FA-MP-DOX polymer was characterized by 1H NMR. ② The cumulative release rates of doxorubicin were 49.1%, 30.3% and 15.3% respectively in PBS buffer system of pH 2.5, pH 5.0 and pH 7.4 for 16 h, confirming the release of doxorubicin in FA-MP-DOX Has pH dependence. ③ cell experiments confirmed FA-MP-DOX cytotoxicity higher than doxorubicin and MP-DOX. Conclusion: FA-MP-DOX polymer drug is expected to become a doxorubicin intelligent controlled release and targeted drug carrier.