天冬酰胺酶-吴茱萸碱核壳型脂质纳米粒的药动学研究

Pharmacokinetic study on asparaginase-evodiamine loaded core-shell lipidic nanoparticles

目的考察天冬酰胺酶-吴茱萸碱核壳型脂质纳米粒(asparaginase-evodiamine core-shell lipidic nanoparticles,AELNs)在大鼠体内的药动学行为,比较AELNs与游离天冬酰胺酶(asparaginase,ASNase)/吴茱萸碱(evodiamine,EVO)的生物利用度。方法取18只SD大鼠,分别尾静脉注射AELNs、游离ASNase和游离EVO,给药后于不同时间点大鼠眼眶取血,分别采用Nessler试剂比色法和HPLC法测定血浆样品中ASNase和EVO的浓度,采用DAS(2.1.1版)软件计算药动学参数。结果将游离ASNase制备成AELNs后,其药时曲线下面积和平均滞留时间分别提高了1.83倍和1.94倍。AELNs中EVO的药时曲线下面积约为游离EVO的28.94倍。结论AELNs提高了ASNase和EVO在大鼠体内的生物利用度。

Aim To investigate the pharmacokinetic behavior of core-shell lipidic nanoparticles(AELNs)loaded with asparaginase and evodiamine in rats, and compare the bioavailability of AELNs with free asparaginase(ASNase)/evodiamine(EVO). Methods Eighteen male Sprague-Dawley rats were randomly divided into three groups and injected with AELNs, free ASNase and free EVO, respectively. After injection, blood samples were taken from the eyelids of rats at different time. The concentration of EVO and ASNase in plasma samples was determined by HPLC and Nessler reagent colorimetry method, respectively. To analyze the differences in pharmacokinetic behavior between AELNs and free ASNase or EVO, their pharmacokinetic parameters were calculated using DAS software. Results AUC (0~48 h) and MRT (0~48h) of ASNase in AELNs were 1.83 and 1.94 times higher than those of free ASNase, respectively. The AUC (0~48 h) of EVO in AELNs was 29.94 times that of free EVO. Conclusions Compared with free ASNase and EVO, AELNs have a higher bioavailability in rats.