两性霉素B聚氰基丙烯酸正丁酯纳米粒跨血脑屏障及抗隐球菌效力的研究  

Efficacy of Amphotericin B-polybutylcyanoacrylate Nanoparticles against Cryptococcal Meningitis in Mice

作　　者：徐楠[1] 邹豪[2] 温海[1] 徐红[1] 仇芸[1] 赵谨[1] 陈江汉[1] 

机构地区：[1]第二军医大学长征医院皮肤科,上海200003 [2]第二军医大学药学院药剂学教研室,上海200433

出　　处：《中国生物医学工程学报》2009年第2期285-288,共4页Chinese Journal of Biomedical Engineering

基　　金：上海市科委纳米专项基金资助项目(0452nm016)

摘　　要：制备携载两性霉素B的聚氰基丙烯酸正丁酯纳米粒(AmB-PBCA-NP),研究其对血脑屏障的透过能力及对隐球菌性脑膜脑炎小鼠的治疗效果。孵化法制备AmB-PBCA-NP,聚山梨酯-80表面修饰,采用高效液相法检测小鼠脑组织中的药物浓度,建立隐球菌性脑膜脑炎小鼠动物模型,比较不同制剂治疗后的脑膜脑炎小鼠生存率及脑内真菌感染情况。AmB组小鼠脑内未能检测出药物,AmB-PBCA-NP组小鼠30 min即可测得浓度,3 h后达(132.52±3.67)ng/g,明显高于同期AmB-L脑内浓度;经AmB-PBCA-NP治疗的脑膜脑炎小鼠生存率显著提高,同时脑内染菌量下降。聚山梨酯-80修饰的AmB-PBCA-NP具有脑靶向作用,对隐球菌性脑膜脑炎具有显著治疗作用。The aim of this study is to investigate the treatmental efficacy of amphotericin B-polybutylcyanoacrylate nanoparticles（AmB-PBCA-NP） in mice with cryptococcal meningitis. AmB-PBCA-NP was prepared by incubation followed with polysorbate 80 modification. High-performance liquid chromatography （HPLC） method was established to determine the concentration of AmB in brain tissue of mice. The efficacy of intravenously administered AmB-PBCA- NP for the treatment of experimental cryptococcal meningitis was compared with that of AmB-L. AraB failed to be detected in brain. In AmB-PBCA-NP group, great concentration was detected after 30min of injection, while the peak [ （132.52 ± 3.67）rig/g] appeared at 3 h, which were significantly higher than those in AmB-L group. Twenty days after the cessation of therapy, the survival rate of mice in AmB-PBCA-NP group（80 % ） was much higher than that in AmB（0） or AmB-L group（60% ）, while the numbers of CFU remaining in the brain were severely lower. AmB- PBCA-NP modified by polysorbate 80 has the potential to transport AmB across the blood brain barrier and treat cryptococcal meningitis in mice.

关 键 词：隐球菌性脑膜脑炎 两性霉素B 聚氰基丙烯酸正丁酯 脑靶向 

分 类 号：R318.08[医药卫生—生物医学工程]