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。
OBJECTIVE To prepare luteolin-loaded Solutol hs15/Poloxamer188 mixed micelles, evaluate their pharmaceutical property and study their anti-tumor activity. METHODS The luteolin-loaded mixed micelles were prepared by thin-film hydration method. The panicle size was measured by laser granulometry, and the morphology was observed under transmission electron micro- scope （TEM）. The in vitro release behavior was determined by the dialysis method. Cell toxicity and uptake assays were employed to evaluate the anti-tumor activity. The targeting effect was studied by fluorescence labeling. RESULTS The prepared luteolin-loaded mixed micelles showed spherical and regular shape with an average particle size of 66. 43 nm and its entrapment efficiency was more than 80%. The 12 h-accumulated release ratio in vitro was up to 97.42%. The cytotoxicity of luteolin-loaded mixed micelles on human lung adenocarcinoma cell line A549 was significantly stronger than that of free luteolin and the uptake rate was improved. After injecting DiR-loaded mixed micelles into nude mouse, the drug begun to accumulate in tumors after 2 h and reached the highest concentration at 6 h which was significantly higher than that in other tissues. There remained strong drug distribution in the tumors after 12 h. CONCLUSION The Solutol hslS/Poloxamer188 mixed micelles have small panicle size and high entrapment efficiency and can en- hance cell toxicity and uptake with certain passive targeting effect. It is a promising delivery system for anti-tumor drug.
出处
《中国药学杂志》
CAS
CSCD
北大核心
2015年第15期1330-1334,共5页
Chinese Pharmaceutical Journal
作者简介
魏平平，女，硕士研究生研究方向：药剂学
通讯作者：徐群为，男，教授，博士生导师研究方向：药剂学E-mail：xuqunwei2015@163．com
贾晓斌，男，研究员，博士生导师研究方向：中药学Tel：（025）85608672E-mail：jiaxiaobinpharmacy@163．com
