脂质体对7-乙基-10-羟基喜树碱稳定性影响

目的考察脂质体对7-乙基-10-羟基喜树碱(7-ethyl-10-hydroxycamptothecin,SN-38)活性形式的保护作用。方法建立测定SN-38活性形式的HPLC法,考察不同pH条件对SN-38活性与SN-38非活性形式相互转变动力学和平衡比例的影响;并研究了37℃的pH 7.4、8.0、9.0、10.0条件下脂质体对SN-38活性形式的保护作用。结果在pH<4.3的条件下,SN-38以其活性形式存在;在pH>9的条件下,SN-38主要以其非活性形式存在;在pH 6.5的条件下,SN-38活性和非活性形式之间相互转换最慢。包裹在脂质体内的SN-38在模拟生理条件下8 h活性形式质量分数仍大于98%。结论脂质体能够有效地保护SN-38α-羟基内酯环。

Effect of liposomes on stability of 7-ethyl-10-hydroxycamptothecin

Objective To study the protection effect of liposome on lactone ring of 7-ethyl-10-hydroxycamptothecin(SN-38).Methods The interconversion kinetics and equilibrium ratio of SN-38 active and inactive forms(SN-38I)under different pH conditions were investigated with an HPLC method,which was developed for simultaneous quantification of SN-38 active and inactive forms in the liposomes.The concentration and equilibrium ratio of active form were measured under different pH including pH 7.4,pH 8.0,pH 9.0,pH 10.0 at 37 ℃.Results SN-38 was existed in the active form at pH of less than 4.3 and mainly in the inactive form at pH of greater than 9.0.The rate of interconversion between active and inactive form was minimum at pH 6.5.Moreover,the active form ratio of encapsulated SN-38 in liposomes was more than 98% under simulated physiological condition in 8 hours.Conclusions The α-hydroxy lactone ring of SN-38 can be effectively stabilized by liposome.