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

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.