阿米替林聚氰基丙烯酸正丁酯纳米粒在大鼠体内药动学与组织分布学分析

Pharmacokinetics and tissue distribution analysis of amitriptiline polybutylcyanoacrylate nanoparticles in rats

目的探讨阿米替林聚氰基丙烯酸正丁酯纳米粒在大鼠体内的药动学和组织分布学,评估其脑靶向性。方法40只SD大鼠按照随机数字表法分为两组,分别静脉注射阿米替林及阿米替林聚氰基丙烯酸正丁酯纳米粒,应用高效液相色谱测血液及组织中不同时间点阿米替林浓度并进行统计分析。结果纳米粒组中阿米替林在大鼠体内的半衰期、平均驻留时间、血药浓度时间曲线下面积分别是普通组的1.43、1.44、1.19倍;在大鼠靶向性评价中,脑组织相对摄取率为4.66;阿米替林组脑靶向效率均<1,提示脑组织分布最低;而阿米替林聚氰基丙烯酸正丁酯纳米粒组脑靶向效率均>1,提示脑组织分布最多。结论阿米替林聚氰基丙烯酸正丁酯纳米粒药动学参数改变明显,具有明显的脑靶向性。

Objective To investigate the pharmacokinetics and tissue distribution of amitriptiline polybutylcyanoacrylate nanoparticles(AMI-PBCA-NP)in rats and evaluate their brain targeting.Methods A total of 40 SD rats were divided into two groups according to the random number table method.AMI-PBCA-NP was injected intravenously.High Performance Liquid Chromatography(HPLC)was used to measure the concentration of amitriptyline in blood and tissues at different time points and perform statistical analysis.[WTHZ]Results The half-life(t_(1/2)),average residence time(MRT_(0-t))and area under the blood concentration time curve(AUC_(0-t))of AMI in the nanoparticles group were 1.43,1.44 and 1.19 times higher than those in the normal group,respectively.In the targeted evaluation of rat brain tissue,the relative uptake rate(Re)was 4.66.In the targeting efficiency(Te),all of the AMI group were less than 1,indicating the lowest brain distribution,while all of the AMI-PBCA-NP group were greater than 1,indicating the largest brain distribution.Conclusions The pharmacokinetic parameters of AMI-PBCA-NP have changed significantly,and they have obvious brain targeting.