去甲斑蝥素N-乳糖酰壳聚糖纳米粒的制备与体外抗肿瘤活性

Preparation and in Vitro Antineoplastic Activity of Norcantharidi N-Associated Galactosylated Chitosan Nanoparticles

目的采用新型壳聚糖载体研究去甲斑蝥素的双重肝靶向制剂。方法以N-乳糖酰壳聚糖为载体,通过离子诱导法,制备去甲斑蝥素N-乳糖酰壳聚糖纳米粒。考察多种制备条件对纳米粒粒径、包封率和载药量的影响。并研究纳米粒冻干粉的体外释放特性、细胞毒性及其与肝肿瘤细胞的亲和性。结果纳米粒外观圆整,粒径较小(118.68±3.37)nm,包封率(57.92±0.40)%,载药量(10.38±0.06)%,体外释药遵循Higuchi方程。与未经半乳糖修饰的壳聚糖纳米粒相比,N-乳糖酰壳聚糖纳米粒在体外对肝肿瘤细胞SMMC-7721、HepG2更具亲和性,细胞毒作用更显著。结论去甲斑蝥素N-乳糖酰壳聚糖纳米粒在体外可发挥双重靶向作用,可显著提高药物的抗肿瘤作用。

OBJECTIVE To investigate a dual hepatocyte-targeting preparation of norcantharidin with model chitosan carder. METHODS Norcantharidin-associated galactosylated chitosan nanoparticles were achieved by ionic cross-linkage process with galactosylated chitosan as carrier. Several factors influencing the particle size, entrapment efficiency, drug-loaded amount of nanoparticles were studied. In addition, in vitro release, cell cytotoxicity and cellular uptake of nanoparticles were also investigated. RESULTS Novel nanoparticles were spherical, average particle size （118.68±3.37） nm, entrapment efficiency （57.92± 0.40） %, drug-loaded amount （ 10.38 ± 0.06 ） %, and in vitro release of nanoparticles lyophilized powder followed Higuchi equation. Compared with chitosan nanoparticles, galactosylated chitosan nanoparticles showed strong cytotoxicity and compatibility with hepatoma cells SMMC-7721 and HepG2. CONCLUSION As dual hepatocyte-targeting carrier, galactosylated chitosan nanoparticles were hopeful for the clinical application.