肝靶向去甲斑蝥素修饰物的合成及其纳米粒的制备  

Synthesis of Hepatocyte-Targeting Norcantharidin Prodrug and Preparation of Its Nanoparticles

作　　者：胡展红[1] 章良[1] 周奕[1] 张学农[1] 

机构地区：[1]苏州大学药学院药剂学教研室,江苏苏州215123

出　　处：《中国药学杂志》2009年第9期679-684,共6页Chinese Pharmaceutical Journal

基　　金：国家科技支撑计划课题资助(2006BAI09B00);国家科技部科技型中小企业技术创新基金(07C26223201333);江苏省"六大人才高峰"资助项目;江苏省卫生厅招标项目(H200630)

摘　　要：目的合成乳糖化-去甲斑蝥素作为主动肝靶向性修饰物,并将其制成纳米粒。方法利用乙二胺为连接臂合成乳糖化-去甲斑蝥素修饰物,并考察其相关理化性质;采用离子诱导法制备乳糖化-去甲斑蝥素壳聚糖纳米粒,以粒径分布、包封率、载药量为综合指标,正交设计优化载药纳米粒的制备工艺,并考察其体外释放特性。结果乳糖化-去甲斑蝥素是一种具有良好水溶性的多羟基化合物,其合成产率为68.35%;经优化工艺制备的乳糖化-去甲斑蝥素的纳米粒的平均粒径(149.46±1.79)nm,包封率(80.29±0.56)%,载药量(9.58±0.09)%,其体外释药遵循Higuchi方程。结论乳糖化-去甲斑蝥素合成简单,产率高,其纳米粒体外释放具有良好的缓释特性。OBJECTIVE To synthesize lactosyl-norcantharidin （Lac-NCTD） as active liver-tageting modified drug and prepare its nanoparticles. METHODS Lac-NCTD was synthesized with ethanediamine as truss arm , and then its properties were studied.Chitosan nanoparticles（CS-NP） were achieved by ionic cross-linkage process with lactosyl-norcantharidin as a model drug. Orthogonal experiment design was applied to optimize the formulation and preparation procedure with particle distribution, entrapment rate and drug-loading rate as integrated indexes. The in vitro release was investigated. RESULTS Lac-NCTD was a kind of polyhydroxy compound and the yield was 68.35%. CS-NP were spherical, average particle size was （149.46± 1.79）nm, entrapment rate was （80.29±0.56） %, drug-loading rate was （9.58±0.09）%, and in vitro release followed Higuchi equation. CONCLUSION The synthesis procedure of Lac-NCTD was simple and the yield was high. Sustained release of CS-NP was identified.

关 键 词：乳糖化-去甲斑蝥素 主动肝靶向 壳聚糖 纳米粒 

分 类 号：R944[医药卫生—药剂学]