Novel albendazole-chitosan nanoparticles for intestinal absorption enhancement and hepatic targeting improvement in rats
Novel albendazole-chitosan nanoparticles for intestinal absorption enhancement and hepatic targeting improvement in rats
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DOI：
10.1002/jbm.b.32908
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发表时间：
2013-08-01
影响因子：
3.4
通讯作者：
Zhang, Xue-nong
中科院分区：
文献类型：
--
作者：
Liu, Yang;Wang, Xiao-qing;Zhang, Xue-nong
为提高对蠕虫病、丝虫病和结直肠癌的治疗效果，以三聚磷酸钠为交联剂，泊洛沙姆188为助溶剂，采用乳化交联挥发法制备了阿苯达唑壳聚糖纳米粒（ABZ-CS-NPs）。使用X-射线衍射法测定纳米颗粒的结构特征，以分析CS与药物之间的相互作用。然后在动物研究中评价NP的理化特性、药物释放行为、体内药代动力学参数和生物分布。具有均匀球形粒径（157.8 +/-2.82nm）的ABZ负载的NP显示出有效的药物负载、包封效率和高物理稳定性。药物从ABZ-CS-NP的释放延长了几个时期。然后拟合动力学模型以确定释放机制。以甲苯咪唑为内标物，采用反相高效液相色谱法测定了大鼠体内阿苯达唑及其代谢产物阿苯达唑亚砜（ABZ-X）的含量。与ABZ混悬液组相比，ABZ和ABD-X的相对生物利用度分别为146.05%和222.15%。此外，血药浓度-时间曲线与血药浓度-时间曲线中的二室模型一致。结果表明，负载ABZ的纳米颗粒是有前途的新型ABZ候选物，用于通过口服给药治疗肝包虫囊肿中的被动扩散。(c)2013 Wiley Periodicals，Inc. J Biomed Mater Res Part A，2013。
To improve the treatment of helminthiasis, filariasis, and colorectal cancer, albendazole-associated chitosan nanoparticles (ABZ-CS-NPs) were prepared using the emulsion crosslinking volatile technique with contained sodium tripolyphosphate as the crosslinking agent and Poloxamer 188 as the auxiliary solvent. The structural characteristics of the NPs were determined using X-ray diffraction to analyze the interaction between CS and the drug. The NPs were then evaluated in terms of their physicochemical characteristics, drug release behavior, in vivo pharmacokinetic parameters, and biodistribution in animal studies. ABZ-loaded NPs with a uniformly spherical particle sizes (157.8 +/- 2.82 nm) showed efficient drug loading, encapsulated efficiency, and high physical stability. The drug release from ABZ-CS-NPs was extended over several periods. Kinetic models were then fitted to determine the release mechanisms. ABZ and its metabolite albendazole sulfoxide (ABZSX) were analyzed in rats with mebendazole as the internal standard using reversed-phase high-performance liquid chromatography. Compared with the ABZ suspension groups, the relative bioavailability values of ABZ and ABZSX were 146.05 and 222.15%, respectively. In addition, the plasma concentration versus time curve is consistent with that of the two compartment models in the plasma concentration versus time curve. The results indicate that the ABZ-loaded NPs are promising novel ABZ candidates for passive diffusion in the treatment of hydatid cysts in the liver via oral administration. (c) 2013 Wiley Periodicals, Inc. J Biomed Mater Res Part A, 2013.