摘要
目的:制备叶酸修饰去甲斑蝥素隐形泡囊新型给药系统,并进行表征及体外药效学评价。方法:采用改良注入法制得新型给药系统,考察其形态、粒径、包封率和体外释放特性等理化性质对其进行表征,并通过它对叶酸受体过度表达Hela细胞的体外细胞摄取试验及生长抑制试验,进行体外药效学评价。结果:研制的隐形泡囊新型给药系统的平均粒径为100.87 nm,包封率为52.3%,体外释放显著缓慢于游离药物,且在模拟正常细胞pH 7.4环境下的释放t1/2是在模拟肿瘤细胞pH 5.0的1.98倍。细胞摄取试验说明叶酸泡囊能提高肿瘤细胞对药物的摄取(P<0.01)。细胞毒性试验证实,叶酸泡囊抑制肿瘤细胞生长的作用显著(P<0.01),但游离叶酸可减轻叶酸泡囊对肿瘤细胞的杀伤作用。结论:本研究采用简单易行的方法制得的叶酸修饰去甲斑蝥素隐形泡囊,体外具有pH敏感性、隐形性、叶酸受体靶向性,是一种具有良好开发前景的主动靶向抗肿瘤新型给药系统。
Objective： To prepare and characterize the novel drug delivery system, norcantharidin-loaded folate-eonjugated stealth niosomes, and to investigate their pharmacodynamic efficacy in vitro. Methods： The novel drug delivery system was prepared by modified injection method, and characterized by evaluation of their physical and chemical properties, such as appearance, particle size, entrapment rate, and in vitro release behavior. Phar- macodynamic evaluation was performed in vitro by cell uptake tests in Hela cells with overexpression of folate recep- tor and growth inhibition tests. Results： The average particle diameter of the norcantharidin-loaded folate-conjuga- ted stealth niosomes was 100.87 nm with an entrapment rate of 52.3%. The in vitro release was significantly slower than that of the free drug. The release t1/2 at pH 7.4 （simulated the normal cell environment） was 1.98 times as large as that at pH 5.0 （simulated cancer cell environment）. Cell uptake tests indicated that they increased the cell uptake of cancer cells towards the drug （P 〈 0.01 ）. Cytotoxicity tests demonstrated that they significantly in- hibited the growth of cancer cells （P 〈 0.01 ）. However, the free folic acid decreased their lethal effect towards cancer cells. Conclusion： The norcantharidin-loaded folate-conjugated stealth niosomes have been prepared with simple and easy procedures. They show features of pH sensitivity, stealth and targeting effect towards folate recep-tor, providing a candidate of novel active targeting anticancer drug delivery system with good prospect.
出处
《中国新药杂志》
CAS
CSCD
北大核心
2013年第18期2174-2178,共5页
Chinese Journal of New Drugs
基金
国家自然科学基金(81273462)
苏州大学自然基金预研项目(Q31320611)
苏州大学大学生创新实验计划项目(11cxxj068)
关键词
去甲斑蝥素
叶酸修饰隐形泡囊
理化性质
体外细胞试验
norcantharidin
folate-conjugated stealth niosomes
physical and chemical properties
in vitrocell study
