木犀草素混合胶束的制备及其抗肿瘤活性研究

发布时间：2018-05-07 02:19

本文选题：木犀草素 + 混合胶束　；参考：《中国药学杂志》2015年15期

【摘要】：目的拟制备载木犀草素的Solutol hs15/Poloxamer188混合胶束系统,对其进行制剂评价,并考察其体外抗肿瘤活性。方法采用薄膜水化法制备木犀草素混合胶束,分别应用激光粒度测定仪和透射电镜对该混合胶束的粒径和形态进行表征,采用透析法评价其体外释放行为,通过细胞毒性和细胞摄取实验考察其体外抗肿瘤活性,并将荧光探针包裹于混合胶束中,探索其在裸鼠体内的靶向效应。结果所制备的木犀草素混合胶束多呈球形,较规则,粒径均一,平均粒径为66.43 nm,包封率大于80%,24 h体外累积释药百分率达到97.42%。木犀草素混合胶束对人非小细胞肺癌A549细胞的细胞毒性显著大于木犀草素原药,细胞对药物的摄取率也有明显提高。活体成像实验结果表明,DiR混合胶束组裸鼠给药后,2 h肿瘤出现药物聚集现象,6 h达到最高浓度且明显高于其他组织,12 h肿瘤部位仍有较强的药物分布。结论 Solutol hs15/Poloxamer188混合胶束系统的粒径小,包封率高,可增加药物的细胞摄取,增强细胞毒性作用,并具有一定的被动靶向作用,是一种具有应用前景的抗肿瘤药物给药系统。
[Abstract]:Aim to prepare Solutol hs15/Poloxamer188 mixed micelle system carrying luteolin, evaluate its preparation and investigate its antitumor activity in vitro. Methods the mixed micelles of luteolin were prepared by membrane hydration method. The particle size and morphology of the mixed micelles were characterized by laser particle size analyzer and transmission electron microscope, and the release behavior in vitro was evaluated by dialysis method. The antitumor activity in vitro was investigated by cytotoxicity and cell uptake tests, and the fluorescent probe was encapsulated in the mixed micelle to explore its targeting effect in nude mice. Results the mixed micelles of luteolin prepared were spherical, regular and uniform in size, the average particle size was 66.43 nm, the encapsulation efficiency was more than 80% and the cumulative drug release percentage reached 97.42% in vitro for 24 h. The cytotoxicity of luteolin mixed micelles to human non-small cell lung cancer A549 cells was significantly higher than that of luteolin. The results of in vivo imaging showed that drug aggregation occurred in nude mice at 2 h after administration of DiR mixed micelle and reached the highest concentration at 6 h, and was significantly higher than that in other tissues at 12 h, and there was still a strong drug distribution in the tumor site. Conclusion the Solutol hs15/Poloxamer188 mixed micelle system has small particle size and high encapsulation efficiency, which can increase the cell uptake and cytotoxicity of the drug, and has a certain passive targeting effect. It is a promising antitumor drug delivery system.
【作者单位】：南京医科大学;江苏省中医药研究院国家中医药管理局中药释药系统重点研究室;宿迁市第一人民医院;
【分类号】：R943;R96

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