mPEG-g-Dex微凝胶偶联羟基喜树碱的制备及性质  

Preparation and Properties of Conjugate of Dextran Coupled with Hydroxycamptothecin

作　　者：刘璐[1] 姚日生[1,2] 尤启冬[2] 陶丽[1] 

机构地区：[1]合肥工业大学化学工程学院,安徽合肥230009 [2]中国药科大学药学院,江苏南京210009

出　　处：《高分子材料科学与工程》2011年第4期143-146,150,共5页Polymer Materials Science & Engineering

摘　　要：以大分子右旋糖酐(Dex)为载体,丁二酸酐(SA)为交联剂,二环己基碳化亚胺(DCC)为缩合剂制备右旋糖酐基微凝胶,同步接枝单甲氧基聚乙二醇(mPEG)、偶联羟基喜树碱(HCPT)-丁二酸单酯。结果表明,缩短了反应时间;mPEG-g-Dex微凝胶偶联HCPT形成了内疏水外亲水的胶束结构,粒径分布在200nm^300nm,可实现对肿瘤组织的被动靶向富集;羟基喜树碱在水中的溶解度由3.9μg/mL提高到400μg/mL,水溶性增加了约100倍,有利于生物利用度的提高;在pH=7.4缓冲溶液中的释放符合Rc=100t1.96/(1166.71+0.08t3.08)动力学方程,20h内偶联物释放HCPT只有20%左右,呈现显著缓释特性。A drug delivery system of dextran（Dex） coupled with hydroxycamptothecin-succinic anhydride（HCPT-SA） monoester and grafted with monomethoxypoly（ethylene glycol）（mPEG）,crosslinked with SA was designed and prepared in the presence of dicyclohexyl carbon imine（DCC） as the condensation agent.The results show that the reaction time has been shortened.The conjugate could assemble to micelle with the diameter of 200 nm～300 nm in water which can be achieved for passive targeting of tumor tissue concentration.The solubility of original drug in water has increased by 100 times from 3.9 μg/mL to 400 μg/mL,that can be conducive to improve the bioavailability of HCPT.The drug release processes accorded with kinetics equation Rc=100t1.96/（1166.71＋0.08t3.08） in the pH7.4 buffer solution.The cumulative release percentage is only 20% within 20h,showing a significant slow-release property.

关 键 词：微凝胶 偶联物 制备 体外释放 右旋糖酐 羟基喜树碱 单甲氧基聚乙二醇 

分 类 号：R979.1[医药卫生—药品]