中文摘要：

目的构建长春新碱抗耐药性隐形脂质体,并考察其在大鼠体内的药动学。方法采用硫酸铵梯度法制备长春新碱抗耐药性隐形脂质体;将Sprague-Dawley大鼠分成两组,分别尾静脉注射长春新碱抗耐药性隐形脂质体和游离药,用高效液相二极管阵列色谱法和高效液相荧光色谱法分别测定血浆中长春新碱和奎纳克林的浓度,通过与游离药组比较,评价长春新碱抗耐药性隐形脂质组的药动学特点。结果长春新碱抗耐药性隐形脂质体的粒径为135.9±7.1nm,其中,长春新碱的包封率大于90%,奎纳克林的包封率大于85%;大鼠尾静脉注射长春新碱抗耐药性隐形脂质体后,与游离药组相比,长春新碱和奎纳克林的血液滞留时间明显增长,并且两者平均血药浓度都明显提高。在长春新碱抗耐药性隐形脂质体组中,长春新碱和奎纳克林的Cmax,t1/2和AUC0-24h都分别高于游离药组的相应值,然而,长春新碱和奎纳克林的Cl都明显低于游离药组的值。结论本研究成功构建了具有高包封率的长春新碱抗耐药性隐形脂质体。抗耐药性隐形脂质体明显延了长春新碱和奎纳克林在血液中的循环时间并提高了二者血浆中平均血药浓度。

英文摘要：

Aim The objectives of the present study were to prepare stealthy vincristine plus quinacrine liposomes and evaluate the pharmacokinetics in Sprague-Dawley rats. Methods Anti-resistant stealthy liposomes were prepared by incorporating vincristine with quinacrine together using the ammonium sulfate gradient loading procedure. For the pharmacokinetic study, Sprague-Dawley rats were divided into two groups： each rat in the Group Ⅰwas administered intravenously via tail vein as stealthy liposomal vincristine plus quinacrine, and the Group Ⅱ similarly given as a mixture solution of free vincristine plus free quinacrine. The concentrations of vincristine and quinacrine in plasma were measured by HPLC with diode array detection and fluorescence detection, respectively. Results The mean particle size of stealthy liposomes was 135.9 ±7.1 nm and the encapsulation efficiencies of stealthy liposomes were 〉 90% for vincristine, and 〉 85% for quinacrine, respectively. Administered as the stealthy vincristine plus quinacrine liposomes, the plasma exposures of both vincristine and quinacrine were significantly extended, and the mean concentrations of both vincristine and quinacrine were significantly higher compared to those given as the mixture solution of free vincristine plus free quinacrine. The Cmax, t1/2, AUC0-24 h values of vincristine for stealthy liposomal group were significantly increased, but the total clearance Cl values decreased, as compared to those of free drug group, respectively. Similarly, the Cmax, t1/2 and AUC0-24 h values of quinacrine for the stealthy liposomal group were significantly increased, but the total clearance C1 values decreased, as compared to those of free quinacrine. Conclusion The anti-resistant stealthy liposomes are successfully prepared by incorporating vincristine with quinacrine, and the liposomes extend significantly the duration in blood circulation and improve evidently the plasma concentrations of both vincristine and quinacrine.