果胶-阿霉素轭合物的合成与淋巴靶向性研究  

Preparation and Lymphatic Targeting Research of Targeting Antitumor Drug:Pectin-Adriamycin Conjugates

作　　者：成明[1,2] 谢萍[3] 唐小海[2] 张杰[4] 谢永美[1,5] 郑开波[1] 何俊[1,2] 

机构地区：[1]四川大学化学学院,成都610064 [2]重庆莱美药业有限公司-四川大学联合药物实验室,成都610207 [3]四川大学华西口腔医学院,成都610041 [4]四川大学华西医院,成都610041 [5]四川大学化学工程学院,成都610065

出　　处：《生物医学工程学杂志》2009年第3期569-574,共6页Journal of Biomedical Engineering

基　　金：重庆市科技计划创新药物专项基金资助项目(CSTC2005AA5007-3)

摘　　要：选用生物多糖-果胶(P)作为药物载体,以酰胺键形式与阿霉素(A)偶联合成了果胶-阿霉素轭合物(P(A)n),通过紫外、红外光谱进行了结构验证,并研究了果胶自身特性以及载药量对P(A)n淋巴靶向性效果的影响。高酯果胶脱酯化研究表明,酯化度(DE)的改变对其羧基含量、特性黏度、半乳糖醛酸含量的影响显著;键接药物阿霉素后,体外释放试验表明,P(A)n在生理盐水中稳定,而在血浆、淋巴中可被酶逐渐水解释放出阿霉素,具有缓释作用;淋巴靶向性试验表明,脱酯果胶酯化度及其载药量对P(A)n淋巴靶向性效果的影响显著。以碱法脱酯120min的果胶为药物载体,载药量为27.9%的P(A)n淋巴靶向性效果最好,局部注射后,淋巴与血中阿霉素的浓度比高达208倍,具有较好的淋巴靶向性。Pectin, a polysaccharide extracted from the cell wall of plants, was used as the drug carrier to synthesize the pectin-adriamycin conjugates（P（A）.）. The structure of the conjugates was confirmed by UV and IR. The degree of esterification（DE） of the pectin was assessed, and it was found that DE significantly influenced the carboxy group contents, inherent viscosity and galacturonic acid contents of the pectin. The results of drug release test in vitro showed that the conjugate was stable in normal saline, but was gradually enzymolyzed to release the adriamyein in blood plasma and in lymph nodes. The results of lymphatic targeting study of P（A）n demonstrated that the modification of DE or drug coupling capacity of pectin significantly influenced the lymphatic targeting characteristics of P （A）n. The adriamyein concentration of lymph nodes was 208 times higher than that of plasma after local injection of the P（A）n, of which the adriamycin content was 27.9%and the pectin was deesterificated 120 minutes by the use of hypothermy alkaline deesterification method.

关 键 词：果胶-阿霉素轭合物脱酯特性黏度 淋巴靶向性 

分 类 号：R94[医药卫生—药剂学] R914[医药卫生—药学]