自组装Tween 20-SDS纳米混合胶束提高普罗布考口服吸收的研究  

Effect of Self-assembled Tween 20-SDS Nanometric Mixed Micelles Loaded with Probucol on Improvement of Oral Absorption

作　　者：王一鑫[1] 蒋世军[2] 黄健[2] 王玲娇[3] 孙国祥[1] 

机构地区：[1]沈阳药科大学药学院,辽宁沈阳110016 [2]中国科学院上海药物研究所,上海201203 [3]河北医科大学第一医院,河北石家庄050000

出　　处：《中国医药工业杂志》2013年第6期571-575,共5页Chinese Journal of Pharmaceuticals

基　　金：国家重大科学研究计划(2009CB930304)

摘　　要：利用Tween-20与十二烷基硫酸钠的两亲性结构,与普罗布考混合,通过自组装技术制备了具有核-壳结构的纳米混合胶束,其中药物浓度可达到20 mg/ml。所得制品平均粒径为(44.6±1.6)nm,多分散系数为0.179±0.058,且用不同pH介质稀释后粒径未发生显著变化。采用共聚焦显微成像技术观察表明,制品能影响Caco-2细胞骨架蛋白,增强细胞膜流动性。建立了UPLC-UV法测定生物样品中普罗布考的浓度。Caco-2细胞单层模型的细胞摄取试验和大鼠体内药动学研究均表明,本品可显著提高普罗布考的口服吸收。Amphiphilic Tween-20 and sodium dodecyl sulfate （SDS） were mixed with probucol to prepare the nanometric mixed micelles with nuclear-shell structure by a self-assembly technique, in which probucol concentration could reach 20 mg/ml. The average particle size was （44.6±1.6）nm with PDI of 0.179±0.058, which had no significant changes after diluted by agents of different pH. The effects of the product on skeleton proteins of Caco-2 cells was observed using laser confocal scan microscopy technique, and the results showed that the product could affect the skeleton proteins and enhance the mobility of cell membrane. An UPLC-UV method was established to measure probucol concentration in biological samples. The results of uptake with Caco-2 cell monolayer model and pharmacokinetics in rats showed that the product could significantly improve the oral absorption of slightly soluble probucol.

关 键 词：普罗布考 自组装纳米混合胶束 UPLC-UV 口服吸收 

分 类 号：R944.9[医药卫生—药剂学]