聚酰胺-胺型树状大分子的甲氨蝶呤体外释放行为的研究  

Study on the Release Behaviors of MTX from PAMAM Dendrimer in Vitro

作　　者：杨华[1] 王颖[1] 苏健婷[1] 王良海[1] 朱莹[1] 唐静成[1] 

机构地区：[1]首都医科大学化学生物学与药学院

出　　处：《首都医科大学学报》2005年第4期443-446,共4页Journal of Capital Medical University

基　　金：北京市科技新星计划(954812000);北京市教委科技发展计划(00KJ-107)资助项目

摘　　要：目的探讨了聚酰胺-胺(PAMAM)树状大分对抗癌药物甲氨蝶呤体外释放作用及其释放机制。方法采用紫外分光光度法测定G(代)4.0PAMAM树状大分子对抗癌药物甲氨蝶呤(MTX)的复合和缓释作用。用磁共振谱和氢谱探讨其复合的机制。结果G4.0PAMAM树状大分子能复合14个MTX分子;G4.0PAMAM树状大分子-MTX复合物在10mmol/LTris-HCl溶液中释放80%MTX需要200h,缓释效果是对照(游离MTX)的10倍;随着介质浓度的增加,G4.0PAMAM树状大分子-MTX复合物缓释效果降低,其稳定性也降低。结论1HNMR和13CNMR数据表明G4.0PAMAM树状大分子与MTX通过PAMAM树状大分子氨基阳离子与MTX羧基阴离子之间的静电作用而形成复合物。Objective Dendrimer, a new class polymeric materials of highly branched, symmetric and nanoscale, are considered as potential drug delivery vehicle for their particular structure and character. The capability of G4.0 Polyamidoamie （PAMAM） dendrimer as anticancer drug methotrexate （MTX） carrier were studied. Methods UV has been employed to monitor the in vitro release of MTX from G4.0 PAMAM in different buffers. We discuss mechanism of complex by ^1H and ^13C NMR. Results Each G4.0 PAMAM could conjugated 14 MTX molecules; An electronic interaction between G4.0 PAMAM primary amine groups and MTX carboxylic groups was demonstrated by ^1 H and ^13C NMR. It took 200 h to release 80 % MTX from the G4.0 PAMAM- MTX complex in 10 mmol/L, pH 7.4 Tris-HCl buffer solution, while 20 h for pure MTX under same condition; With the increasing of ionic strength in Tris-HCl buffer solution, the G4.0 PAMAM-MTX complex released MTX fast and the stability of theG4.0 PAMAM-MTX system decreased. Conclusion ^1H and ^13C NMR data demonstrated the interaction between G4.0 PAMAM dendrimer primary amine groups and MTX carboxylic groups is due to the electrostatic force; G4.0 PAMAM dendrimer could load 14 MTX molecules; the controlled release ability of G4.0 PAMAM-MTX complex was 10 times better than the control （pure MTX） in 10 mmol/L（pH 7.4） Tris-HCl buffer solution.

关 键 词：G4.0PAMAM树状大分子 甲氨蝶呤 复合 缓释 

分 类 号：R91[医药卫生—药学]