毛萼乙素长循环脂质体的制备与大鼠体内药动学研究

Preparation of Eriocalyxin B-loaded PEGylated Liposomes and Pharmacokinetics in Rats

目的制备毛萼乙素长循环脂质体(EriB-Lips)并评价其在大鼠体内药动学。方法采用乙醇注入法制备EriB-Lips,通过透射电子显微镜观测EriB-Lips的微观形态,测定EriB-Lips的粒径分布、Zeta电位、包封率和载药量,考察EriB-Lips体外释药行为,评价EriB-Lips在大鼠体内药动学行为。结果通过透射电镜可以观察到EriB-Lips的磷脂双分子层结构,呈球形或类球形,平均粒径为(106.3±7.7)nm,Zeta电位为(-6.2±0.3)mV,包封率为(85.5±0.8)%,载药量为(9.8±0.7)%;与EriB乙醇溶液相比EriB-Lips体外释药缓慢,释放行为符合一级动力学方程;大鼠药动学研究结果表明EriB-Lips的T1/2、Cmax和AUC0-∞分别是EriB乙醇溶液的3.76、2.10和5.20倍。结论本研究将毛萼乙素制备成长循环脂质体延长药物在大鼠体内的循环时间,提高药物生物利用度,可增强药物治疗效果。

Objective To prepare Eriocalyxin B-loaded PEGylated liposomes(EriB-Lips)and evaluate their pharmacokinetics in rats.Methods EriB-Lips were prepared using the ethanol injection method.The morphology,particle size distribution,zeta potential,encapsulation efficiency and drug loading of EriBLips were measured.The drug release behavior of EriB-Lips in vitro was investigated.The pharmacokinetics of EriB-Lips in rats was evaluated.Results The phospholipid bilayer structure of EriB-Lips could be observed by transmission electron microscopy with a spherical or spheroidal distribution.The average particle size was(106.3±7.7)nm and the zeta potential was(-6.2±0.3)mV.The encapsulation efficiency was(85.5±0.8)%and the drug loading was(9.8±0.7)%.EriB-Lips were slowly releasedin vitro compared with EriB solution,and the release behavior complied with the first-order kinetic equation.The pharmacokinetics showed that the T1/2,Cmaxand AUC0-∞ of EriB-Lips were 3.76-times,2.10-times and 5.20-times those of EriB solution,respectively.Conclusion EriB-Lips can prolong the circulation time in vivo and improve bioavailability,which can contribute to the therapeutic effect of EriB.