阿苯达唑葡聚糖纳米颗粒大鼠体内药动学和小鼠肝脏靶向性研究

目的:以葡聚糖纳米颗粒(glucan particles,GPs)负载阿苯达唑(albendazole,ABZ)得到的阿苯达唑葡聚糖纳米颗粒(ABZ-GPs)为研究对象,探索其在大鼠体内药动学特征及对小鼠肝脏的靶向性.方法:大鼠和小鼠分别灌胃给予ABZ和ABZ-GPs,并于给药后不同时间点从大鼠眼脉络丛取血、小鼠解剖取...

Pharmacokinetics and liver targeting ability of albendazole-glucan particles

OBJECTIVE Glucan particles(GPs) are used for preparing albendazole-GPs(ABZ-GPs) to study the pharmacokinetics of albendazole-glucan particles in rats and liver distribution specificity in mice.METHODS Rats and mice were administrated albendazole and albendazole-glucan particles by gavage, respectively.Blood taken from the choroid plexus of the rat eyes and the liver was obtained from the mice at different time points after the administration.After the liver and blood samples were processed with different methods, LC-MS/MS was used to measure the drug concentration in these samples, and the pharmacokinetic parameters as well as the liver targeting ability of the two drugs were analyzed.RESULTS The established LC-MS/MS method had a good linear relationship in the determination of drug content in plasma and liver tissue.The intra-day and inter-day precision and stability RSD of the standard product was less than 11%, and the recovery rate of the extraction method was more than (83.85±0.91)%.The pharmacokinetic parameters of the active-components-albendazole sulfoxide from the ABZ-GPs were C_max=(0.86±0.07) μg·h·mL^-1, t_max=(8.00±0.35) h, AUC_0-t=(8.60±1.72) μg·h·mL^-1, MRT_0-t=(7.00±0.87) h;the maximum of ABZSO concentration ratio(Ce) of ABZ-GPs/ABZ in mouse liver tissue was 1.32, and the targeting index(TI) of ABZ-GPs/ABZ was 3.27.CONCLUSION Compared to the original drug albendazole, albendazole-glucan particles were absorbed more quickly in rats, also has better-liver targeting ability and obvious sustained-release effects in mice.