聚苹果酸-羟喜树碱前药的合成和性质初探  

Prodrug of Poly(β-malic acid)-Hydroxycamptothecin Polymer:Preparation,Characterization and Biological Evaluation

作　　者：乔友备[1] 张海涛[2] 李飞[1] 李伟[1] 段晓[1] 成冲[1] 陶阳春[1] 吴红[1] 

机构地区：[1]第四军医大学药学院药物化学教研室,陕西西安710032 [2]西北工业大学理学院,陕西西安710072

出　　处：《现代生物医学进展》2012年第17期3253-3258,共6页Progress in Modern Biomedicine

基　　金：国家自然科学基金项目(30970788)

摘　　要：目的:化学全合成聚苹果酸(poly(β-malic acid),PMLA),将其作为高分子药物载体,制备聚苹果酸-羟喜树碱前药(PMLA-HCPT)。研究其体外释药特点和体外细胞毒性。方法:以L-天冬氨酸为原料,通过化学方法全合成PMLA,通过酰胺键键合羟基喜树碱(HCPT)。通过红外光谱、核磁共振光谱表征该前药的结构,利用体外动态透析的方法模拟体外释药特点,用高效液相色谱法测定不同pH值聚合物药物中前喜树碱的释药特性。采用人卵巢癌HO-8910细胞系研究该前药的体外毒性。结果:①经核磁共振表征PMLA-HCPT前药合成完成。②在pH 5.6、pH 6.8及pH 7.4的PBS缓冲体系16 h中,羟喜树碱药物累积释放率分别为76.8%,47.2%和18.1%,证实PMLA-HCPT中羟喜树碱的释放具有pH依赖性。③细胞实验证实PMLA-HCPT的细胞毒性和游离的HCPT相比没有降低。结论:PMLA是一种良好的药物载体材料,PMLA-HCPT有望成为具有pH敏感性的聚合物前药。Objective： Poly（beta-malic acid）（PMLA） was synthesized,and used as polymeric drug carrier.A novel poly（beta-malic acid）-hydroxycamptothecin conjugate（abbreviated as PMLA-HCPT） for active tumor targeting was set up.Methods： The structure of this prodrug was confirmed by FT-IR and 1H-NMR.Furthermore,the conjugation efficiency,drug release property of the prodrug was determined.The cytotoxicity were assessed by using human ovarian cancer HO-8910 cell lines as in vitro cell model.Results：（1） The conjugates were prepared successfully.（2） In vitro HCPT release from PMLA-HCPT conjugate occurred at a faster rate at acidic pH compared with neutral pH（7.4）.The released free HCPT after 16 h of incubation at pH 5.6,6.8 and 7.4 was 76.8 %,47.2 % and 18.1 %,respectively.（3）The cytotoxicity of PMLA-HCPT conjugates against HO-8910 cells,were not lower than free HCPT.Conclusion： PMLA is a good drug carrier material.PMLA-HCPT conjugate could be used as a promising hydroxycamptothecin carrier.

关 键 词：聚合物药物 聚苹果酸 羟喜树碱 药物转运系统 

分 类 号：R284.3[医药卫生—中药学] R944.2[医药卫生—中医学]