18α-甘草酸固体脂质纳米粒的药动学研究

Pharmacokinetics Study of 18α-GL Solid Lipid Nanoparticles

目的对18α-GL固体脂质纳米粒(18α-GL-SLN)的药动学进行研究。方法在大鼠股静脉和肝脏同时植入探针,尾静脉给药后,同步微透析采样10 h,HPLC测定透析液中18α-GL的浓度,推算血液及肝脏中真实18α-GL药物浓度,拟合药-时曲线,计算药动学参数,并进行统计分析。结果大鼠尾静脉给予18α-GL-SLN和18α-GL后血液和肝脏的主要药动学参数Cmax、AUC0→T(n)、AUCextra和MRT差异均有统计学意义。与18α-GL水溶液相比,18α-GL-SLN的血液Cmax显著降低,肝脏Cmax显著升高,MRT显著延长,AUC显著增高。结论 18α-GL-SLN给药后药物在大鼠肝脏中的浓度显著升高,存留时间显著延长,提示18α-GL-SLN具有显著的肝脏靶向特性。

ABSTRACT： OBJECTIVE To study the pharmacokinetics of 18α-GL solid lipid nanoparticles（18α-GL-SLN）. METHODS Implanted microdialysis probes into the femoral vein and liver of rats, and sampling at the same time for 10 h after 18α-GL-SLN and 18α-GL solution administration. Dialysate was determined with HPLC and real 18α-GL drug concentration in blood and liver was calculated. Drug-time curve was fitted, pharmacokinetics parameters were calculated and these parameters were compared by statistical analysis. RESULT Pharmacokinetics parameters of Cmax, AUC0→T, AUCextra and MRT were significantly different in blood and liver after 18α-GL-SLN and 18α-GL administration. Compared wih 18ct-GL solution, 18α-GL-SLN had lower Cmax in blood, higher Cmax, longer MRT and higher AUC in liver. CONCLUSION Concentration of 18α-GL in liver increases significantly and the MRT becomes longer after 18α-GL-SLN administration. Experiment shows that 18α-GL-SLN has distinguished liver target characteristics.