毛兰素固体脂质纳米粒药动学与组织分布学研究

A study on pharmacokinetics and tissue distribution of solid lipid nanoparticles of erianin

目的:研究毛兰素固体脂质纳米粒(erianin solid lipid nanoparticles,ER-SLN)在大鼠中的药动学行为以及在小鼠体内的组织分布。方法:制备ER-SLN,大鼠静脉注射毛兰素混悬液(free ER)及ER-SLN,小鼠静脉注射free ER及ER-SLN,HPLC法测定各组织(血浆、心、肝、脾、肺、肾、脑)中的毛兰素含量,对测得的数据应用统计学软件进行统计分析。结果:静脉注射后ER-SLN在大鼠体内的AUC_(0-t)、MRT_(0-t)、t_(1/2)分别是free ER组的2.14,1.85,1.46倍;组织分布学考察表明ER-SLN在肝脏中的相对摄取率(Re)最高(1.37),同时ER-SLN在各组织中的靶向效率(Te)均大于1,对肝脏的选择性明显强于free ER。结论:毛兰素制备成纳米粒后能明显延长药物在大鼠体内的平均驻留时间(MRT),增大AUC和C_(max)值,提高生物利用度,同时在小鼠肝脏中能有效富集,减慢在肝脏中的清除速率,具有较明显的肝被动靶向性。

OBJECTIVE To investigate the pharmacokinetic behavior in rats and tissue distribution in mice of solid lipid nanoparticles of erianin(ER-SLN).METHODS ER-SLN was prepared,erianin suspension(free ER)and ER-SLN were injected into rats intravenously,and also into mice intravenously.With HPLC method,ER contents in various tissues(blood plasma,heart,liver,spleen,lung,kidney,brain)were determined,and the obtained data were analyzed statistically with statistic software.RESULTS After intravenous injection,AUC0-t,MRT0-t and MRT t1/2 of ER-SLN were 2.14,1.85 and 1.46 times that of free ER.The study on tissue distribution showed that the relative extraction rate(Re)of the ER-SLN in the liver was the highest(1.37).At the same time,the target efficiency(Te)of ER-SLN in each tissue was greater than 1,and the selectivity of ER-SLN for the liver was significantly stronger than that of the free erianin.CONCLUSION Erianin preparation of SLN can significantly prolong its mean retention time(MRT)in rats,increase the AUC0-t and Cmax values,and improve its bioavailability.Meanwhile,it can accumulate in the liver of mice effectively,retard its clearance rate in the liver,and so has significant passive target for the liver.