二氢杨梅素长循环纳米脂质体的制备及大鼠体内药动学研究  

Preparation of long-circulating dihydromyricetinliposomes and its pharmacokinetics in rats

作　　者：张文娟 陈一桢 唐兰如 刘红[1] 陈勇[1] 

机构地区：[1]湖北大学中药生物技术湖北省重点实验室,湖北大学生物资源绿色转化协同创新中心,湖北武汉430062

出　　处：《中草药》2018年第4期806-813,共8页Chinese Traditional and Herbal Drugs

基　　金：湖北省技术创新专项重大项目(2016ACA140);教育部创新创业联合基金(201601031004)

摘　　要：目的筛选二氢杨梅素(DMY)长循环纳米脂质体的最佳处方和制备工艺,研究其体外释放特性和大鼠体内药动学特征。方法采用薄膜超声法制备脂质体,通过单因素和正交试验优化脂质体处方和制备工艺;采用透射电子显微镜观察脂质体的外观形态,激光粒径分析仪测定脂质体的粒径和Zeta电位;采用透析法研究脂质体体外释放特性,LC-MS/MS法测定大鼠血药浓度。结果优化的DMY脂质体制备条件为大豆磷脂酰胆碱-胆固醇-DSPE-m PEG2000物质的量比为75∶20∶5,DMY与类脂的质量比为1∶12,载药温度为60℃,载药介质为pH 5.0 PBS缓冲液,超声时间为20 min。在此条件下,DMY的包封率为(54.7±3.3)%,载药量为(4.3±0.2)%,粒径为(117.9±5.5)nm,Zeta电位为(-2.6±1.7)m V。48 h在pH 1.2和pH 6.8释放介质中的累积释放率均为86%。DMY脂质体在大鼠体内的t_(1/2z)和AUC0~∞分别是游离DMY的2.7倍和1.8倍。结论与游离DMY相比,DMY脂质体体外释放缓慢,体内消除减缓,口服生物利用度提高。Objective To prepare dihydromyricetin （DMY） long-circulating liposomes and evaluate in vitro release dynamics and in vivo pharmacokinetics in rats. Methods Film-ultrasonic method was used to prepare DMY liposomes by single factor experiment and orthogonal test to optimize the formulation and preparation of DMY liposomes. The particle size and zeta potential of liposomes were determined by laser particle size analyzer. The morphological examination of liposomes was performed by using transmission electron microscopy. The liposome release in vitro was studied using dialysis method. DMY concentration in rat plasma was determined by the established LC-MS/MS method. Results The optimal prescription was 75：20：5 for soybean phospholipid-cholesterol-mPEG 2000-DSPE, and 1：12 for DMY-lipid （wt/wt） with the ultrasonic time of 20 min and loading temperature of 60℃ in pH 5.0 PBS buffer. Under the optimized conditions, DMY liposomes was sphere with mean particle size of （117.9 ±5.5） nm and mean zeta potential of （？2.6 ±1.7） mV, the encapsulation efficiency and drug-loading content was （54.7 ±3.3）% and （4.3 ±0.2）%, respectively. The in vitro accumulative release rate of 48 h was 86% in pH 1.2 and pH 6.8 dissolve medium. Compared with free DMY, the t1/2z and AUC0-∞ of DMY liposome were increased by 2.7-fold and 1.8-fold, respectively. Conclusion Compared with free DMY, DMY liposomes released gently and slowly in vitro, eliminated slowly in vivo, and had higher bioavailability of oral administration.

关 键 词：二氢杨梅素 薄膜超声法 长循环纳米脂质体 累积释放率 药动学 LC-MS/MS 

分 类 号：R283.6[医药卫生—中药学]