【作者】 丁娅； 张鹏； 汤晓燕； 耿冬冬； 张灿；

【Author】 Ya Ding1,Peng Zhang 2,Xiao-Yan Tang, Dong-Dong Geng, Can Zhang1, School of Pharmacy,China Pharmaceutical University,Nanjing 210009 2Institut of Chemistry,Chinese Academy of Sciences,Postal address,City,Post code

【机构】 中国药科大学药学院；

【摘要】 <正>本文为改善天然抗肿瘤活性成份藤黄酸的水溶性,提高其生物利用度,延长体内半衰期等目的,以构建水溶性聚合物聚乙二醇修饰天然抗肿瘤活性成分藤黄酸的前体药物为研究重点,采用三种不同分子量的聚乙二醇为水溶性聚合物载体,以氨基酸和简单的肽类作为连接臂来构建聚乙二醇化藤黄酸高分子聚合物前药。本文共合成了24种藤黄酸前体药物,通过FT-IR,1HNMR和MALDI-TOF进行了结构表征,紫外更多还原

【Abstract】 In this work,for improving water-solubility,circulation time in body,and pharmacokinetic profiles of Gambogic acid,PEG-GA conjugates linked with and without spacers were synthesized.The in vitro drug release,pharmacokinetics,biodistribution,and cell cytotoxicity of PEG-GA conjugates were systematically investigated to demonstrate the importance of molecular weight of polymer and steric hindrance of spacers in the design of macromolecular prodrugs.It was found that the molecular weight of PEG and the choice of spacers played important role in controlling the drug percentage,water solubility,and drug release properties of PEG-GA conjugates with and without spacers.These results demonstrate the polymeric conjugation method,by rational design and component selection,would solve many problems of insoluble chemical and natural anti-cancer agents,and at the same time achieve excellent properties of drug delivery systems.更多还原