齐多夫定棕榈酸酯及其脂质体在小鼠和大鼠血浆中的稳定性

Stabilities of azidothymidine palmitate and its liposome preparations in mice and rats blood plasma

目的研究齐多夫定棕榈酸酯溶液及其脂质体制剂在小鼠和大鼠血浆中的酶降解动力学及其稳定性。方法分别制得齐多夫定棕榈酸酯溶液、齐多夫定棕榈酸酯脂质体和修饰齐多夫定棕榈酸酯脂质体,以HPLC法测定它们在啮齿类动物小鼠和大鼠血浆中的降解情况。结果齐多夫定棕榈酸酯在小鼠和大鼠血浆中的降解均服从表观一级反应,其降解速率常数大小顺序依次为:溶液>脂质体>修饰脂质体;稳定性依次为:修饰脂质体>脂质体>溶液。结论将齐多夫定棕榈酸酯载入脂质体后其血浆中的稳定性显著提高。

Objective To investigate the enzymatic degradation kinetics of azidothymidine palmitate solution and liposome preparations. Methods Azidothymidine palmitate solution, liposomes and modified liposomes were preparaed and their degradations in rodents blood plasma were determinated by HPLC. Results Degradations of azidothymidine palmitate were shown to apparent first-order kinetics in blood plasma of mice and rats, and the rate constants of azidothymidine palmitate solution 〉 liposomes 〉modified liposomes. Conclusions The stability of AZTP in rodents plasma is greatly raised when it is encapsulated in liposomes.