液态复合物载药法制备10-羟基喜树碱白蛋白纳米粒及其初步体内外评价  

Preliminary evaluation of 10-hydroxycamptothecin loaded human serum albumin nanoparticles prepared by drug-liquid compound method

作　　者：杨臻博[1] 龚伟[1] 王志媛[1] 李兵胜[1] 李明媛[1] 谢向阳[1] 张慧[1] 杨阳[1] 梅兴国[1] 

机构地区：[1]军事医学科学院毒物药物研究所,北京100850

出　　处：《国际药学研究杂志》2015年第3期355-361,共7页Journal of International Pharmaceutical Research

基　　金：国家科技重大专项综合性新药研究开发大平台资助项目(2012ZX09301003-001-009)

摘　　要：目的采用液态药物复合物载药法制备10-羟基喜树碱人血白蛋白纳米颗粒(HCPT-HSA-NP),并对其进行体内外评价。方法以低相对分子质量聚乙二醇和10-羟基喜树碱液态药物复合物(l-PEG-HCPT)为基础制备纳米颗粒。对其理化性质进行表征,包括测定纳米粒的包封率、溶液物理稳定性、体外释放以及形态学考察和X线粉末衍射等,并初步考察注射液和该制剂(8 mg/kg)在肿瘤动物模型中的药效学情况。结果制备的载药纳米粒理化参数符合纳米药物基本要求。包封率>99%,溶液稳定性良好;体外释放时间可达100 h。HCPT-HSA-NP组抑瘤率显著高于HCPT注射液组(P<0.01)。结论 l-PEG-HCPT液态药物载药法可用于HCPT-HSA-NP的制备。Objective To ch aracterize and evaluate in vitro and in vivo of the 10-hydroxycamptothecin （HCPT） loaded human serum albumin nanoparticle （HSA-NP） prepared by drug-liquid compound method. Methods The HCPT-HSA-NP was prepared with low weight polyethylene glycol drug-liquid compound and blank albumin nanoparticle. Then the in vitro evaluations were conducted with tests of entrapment efficiency, solution stability, accumulative release, morphous investigation and X-ray powder diffraction. At the same time, the primary pharmacodynamics comparison between HCPT injection and the nano preparation （8 mg/kg） was carried out on animal tumor model. Results The obtained HCPT-HSA-NP fitted to the basal features of nano preparation. The entrapment efficiency was averagely higher than 99% for each sample and the solution was stable. In vitro accumulative release study showed that the preparation had long-term release pattern over 100 hours. In vivo pharmacodynamics study showed that the HCPT-HSA-NP was significantly more effective than HCPT injection （P〈0.01）. Conclusion The drug-liquid compound method can be used to prepare HCPT-HSA-NP.

关 键 词：10-羟基喜树碱 人血白蛋白纳米粒 液态药物复合物 聚乙二醇 包封率 

分 类 号：R943[医药卫生—药剂学]