多西紫杉醇载药纳米微球的制备?表征以及对人卵巢癌SKOV3细胞的体内外抗肿瘤效果评价
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国家重点基础研究发展计划(973计划)(2007CB935702)


In vitro and in vivo evaluation of antitumor effect of drug delivery system of docetaxel against ovarian cancer
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    摘要:

    目的: 制备可生物降解高分子材料作载体的多西紫杉醇载药纳米微球(Doc-np),检测其各项特征,并考察其体内外抗肿瘤效果-方法:采用溶剂分散法制备Doc-np-用原子力显微镜和透射电子显微镜观察Doc-np的形态,并用动态光散射仪测定纳米微球的粒径-通过紫外分光光度法测定并计算得出Doc-np的载药量和包封率,再测定该微球的体外释放曲线-在体外及体内考察Doc-np对人卵巢肿瘤SKOV3细胞系的杀伤效果-结果:Doc-np为不规则的圆形,表面光滑,其包封率在90%以上-体外释放曲线显示了Doc-np良好的缓释特性,由细胞实验结果看出Doc-np在体外的抑瘤效果更强-体内实验显示通过肿瘤局部的针对性给药,Doc-np与Doc相比明显延缓肿瘤的生长,显示出优于裸药的抗肿瘤效果-结论:Doc-np与Doc相比可以明显抑制人卵巢肿瘤的生长-肿瘤局部给药增强了Doc-np的抗肿瘤效果,作为一种更为有效的给药途径值得进一步研究-

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    Objective:To prepare and characterize docetaxel-loaded nanoparticles(Doc-np) and to evaluate antitumor efficiency of Doc-np in vivo and in vitro. Methods: Doc-np was prepared by nano-precipitation method. Particle size was detected by dynamic light scattering,and the form was observed by atom force microscopy and transmission electron microscopy. Drug load content and encapsulation efficiency were measured by UV. In vitro release curve was also spotted. In vitro cytotoxicity was performed by MTT assay. Nude mice with transplanted tumor were used to measure the in vivo antitumor efficiency of Doc-np. Results: It was found in our study that Doc could be incorporated into the nanoparticles with high encapsulation efficiency more than 90%. In vitro release study showed that Doc was released from Doc-np in a sustained manner,and cytotoxicity studies indicated that IC50 of Doc-np against SKOV3 cells was significantly lower than that of free Doc. Furthermore, intratumoral administration was applied to improve the tumor-targeted delivery in the evaluation in vivo. Compared with free Doc, Doc-np exhibited superior antitumor effect by delaying tumor growth when delivered intratumorally. Conclusion: These results suggest that Doc-np are effective to inhibit the growth of human ovarian cancer, and intratumoral delivery of Doc-np could be a clinically useful therapeutic regimen and merit more research to evaluate the feasibility of clinical application.

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仉艳华,张国桃,郑东辉.多西紫杉醇载药纳米微球的制备?表征以及对人卵巢癌SKOV3细胞的体内外抗肿瘤效果评价[J].南京医科大学学报(自然科学版),2010,(11):1551-1555

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  • 收稿日期:2010-06-08
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