脑靶向3′,5′-二辛酰基-5-氟脲嘧啶脱氧核苷药质体研究  

STUDY ON BRAIN TARGETING 3′,5′-DIOCTANOYL-5-FLUORO-2′-DEOXYURIDINE PHARMACOSOMES

作　　者：张志荣[1] 王建新[2] 

机构地区：[1]四川大学华西药学院,四川成都610041 [2]上海市中药研究所,上海200127

出　　处：《药学学报》2001年第10期771-776,共6页Acta Pharmaceutica Sinica

基　　金：国家杰出青年科学基金( 3992 5 0 39);国家自然科学基金( 39970 877);高等学校博士学科点专项科研基金;高等学校骨干教师资助计划项目

摘　　要：目的　为提高氟苷的脑靶向性 ,以增强疗效 ,降低毒副作用 ,制备其前体药物 3′ ,5′ 二辛酰基 氟苷的药质体。方法　用薄膜 超声分散法制备药质体 ,中心组合设计优化制备工艺 ,反向动态透析法测定体外释药情况 ,HPLC法测定小鼠iv后在体内各组织的分布。结果　药质体平均粒径为 76nm ,载药量为 2 9 0 2 % ,包封率为 96 6 2 % ;体外释药过程符合双指数方程 ;以氟苷注射液为对照 ,药物在小鼠脑中靶向指数为对照液的 10 97倍 ;并可显著延长药物在血液中的滞留时间。结论　氟苷酯化前体药物的药质体在体内有良好的脑靶向性 。AIM To investigate the specific brain drug targeting of 5 fluoro 2′ deoxyuridine (FUdR) by synthesis of 3′,5′ dioctanoyl 5 fluoro 2′ deoxyuridine (DO FUdR) and incorporation into DO FUdR pharmacosomes (DO FUdR PS). METHODS DO FUdR PS was prepared by thin layer ultrasonication technique. In vitro drug release was studied in pH 7 4 phosphate buffered saline containing 0 3% pancreatic enzyme at 37℃ using bulk equilirium reverse dialysis bag technique. The concentration of FUdR in various organs were determined by reversed phase HPLC after iv administration of DO FUdR PS and FUdR. RESULTS The mean particle size of DO FUdR PS was 76 nm with drug loading of 29 02% and entrapment efficiency of 96 62%. The in vitro drug release kinetics could be characterized by bioexponential equation. Compared with FUdR injection, DO FUdR PS showed high concentration in tested organs. The brain AUC ratio of DO FUdR PS to FUdR was 10 97. CONCLUSION DO FUdR PS showed a good targeting efficiency in vivo . PS can improve the ability of drug to cross blood brain barrier and is a promising drug targeting system for the treatment of central nervous system disorders.

关 键 词：3′ 5′-二辛酰基-氟苷 药质体 脑靶向给药系统 

分 类 号：R944.9[医药卫生—药剂学]