阿苯达唑-壳聚糖纳米粒的制备及体内外评价  

Preparation of albendazole-chitosan nanoparticles and its characteristics in vivo and in vitro

作　　者：王晓青[1] 顾宗林[1] 袁明月[1] 朱爱军[1] 陈维良[1] 施林森[1] 张学农[1] 任伟新[2] 迪理木拉提.巴吾东 顾俊鹏[2] 许晓东[2] 

机构地区：[1]苏州大学药学院,苏州215123 [2]新疆医科大学附属第一医院,乌鲁木齐830054

出　　处：《中国新药杂志》2013年第7期755-761,共7页Chinese Journal of New Drugs

基　　金：国家"重大新药创制"科技重大专项(2009ZX09310-001);国家自然科学基金(30690102);国家973项目(2009CB930300);国家大学生创新实践课题(111028533);江苏省科技支撑计划(BE2011670)

摘　　要：目的:以阿苯达唑(albendazole,ABZ)为模型药物,壳聚糖为载体,泊洛沙姆188(Poloxam-er188,Po188)为助溶剂,研制阿苯达唑壳聚糖纳米粒(ABZ-CS-NPs),分别对体外药剂学性质和体内药动学及肝靶向性分布进行评价。方法:采用离子交联-挥发法制备纳米粒;动态透析法探究纳米粒的体外释放特性;小动物活体成像技术考察纳米粒的肝靶向性;建立RP-HPLC快速测定血浆中阿苯达唑(ABZ)和阿苯达唑亚枫(ABZSX)含量,3P97程序计算药动学参数。结果:纳米粒平均粒径(155.8±2.82)nm,载药量(13.38±0.44)%,包封率(79.57±0.96)%。纳米粒在不同pH介质中的释放均符合Higuchi方程。大鼠口服纳米后体内阿苯达唑和阿苯达唑亚枫血药浓度经时曲线均符合二室模型,其相对生物利用度分别为原料药混悬剂的146.05%和222.15%。结论:ABZ-CS-NPs形态圆整,粒径分布均匀,在体外具有较好缓释特性和pH敏感性,显著提高了原料药的生物利用度,延长了ABZ和ABZSX的作用时间,显示出良好的肝靶向性。该新型肝靶向纳米药物输送系统具有良好的开发应用前景。Objective： To prepare albendazole-loaded chitosan nanoparticles （ABZ-CS-NPs） by emulsion crosslinking-volatile technique with Poloxamer188 （Po188） as auxiliary solvent, and to evaluate pharmaceutical characteristics in vitro as well as pharmacokinetics and hepatic targeting distribution in vivo, respectively. Meth- ods： Nanopartieles were prepared by emulsion crosslinking-volatile technique. Then, NPs were evaluated in terms of physicochemical characteristics, drug release behavior, in vivo pharmaeokinetie parameters and biodistribution in animal studies. ABZ and its metabolites ABZSX were analyzed by RP-HPLC method in rats with mebendazole （MBZ） as internal standard and its pharmacokinetic parameters were calculated by 3P97 program. Results： Alben- dazole-loaded nanoparticles with an uniformly spherical particle size （ 155.8 ± 2.82） nm showed high loading drug content （ 13.38 ± 0.44） % and encapsulated efficiency （79.57 ± 0.96） % , respectively. Drug release from ABZ- CS-NPs was extended over a period of times and kinetic models were fitted to find out the release mechanisms.Compared with ABZ-suspension groups, the relative bioavailability of ABZ and ABZSX were 146.05% and 222.15%, and the plasma concentration versus time curve accorded with the two compartment model. Conclusion： ABZ-CS- NPs have good stability, excellent repeatability and sustained drug release characteristics. The accumulation of ABZ and ABZSX in the liver shows a prospective of hepatic targeting of the albendazole-loaded nanoparticles for the ef- fective treatment of hydatid cysts in the future.

关 键 词：阿苯达唑 纳米粒 肝靶向性 体内药动学 

分 类 号：R943.42[医药卫生—药剂学] R978.6[医药卫生—药学]