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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。
Objective To construct vincristine resistant stealth liposomes and study its pharmacokinetics in rats. Methods Vincristine antithrombotic liposomes were prepared by ammonium sulfate gradient method. Sprague-Dawley rats were divided into two groups. The vinblastine-resistant stealth liposomes and free drugs were injected through tail vein respectively, The concentrations of vincristine and quinacrine in plasma were determined by liquid chromatography with diode array and high performance liquid chromatography. The pharmacokinetics of vincristine-resistant stealth lipid was evaluated by comparing with that of free drug group Features. Results The vincristine resistant stealth liposomes had a diameter of 135.9 ± 7.1nm. The entrapment efficiency of vincristine was more than 90% and the entrapment efficiency of quinacrine was more than 85%. The tail vein of rat After injection of vincristine resistant stealth liposomes, compared with the free drug group, vincristine and quinacrine blood retention time significantly increased, and both the average blood concentration were significantly increased. In the vincristine resistant stealth liposome group, the Cmax, t1 / 2 and AUC0-24h of vincristine and quinacrine were respectively higher than those of the free drug group, however, vincristine and Cl of quinacrine was significantly lower than that of the free drug group. Conclusion The vincristine resistant stealth liposome with high encapsulation efficiency was successfully constructed in this study. Anti-drug-resistant stealth liposomes significantly delayed the circulating time of vincristine and quinacrine in the blood and increased the plasma mean plasma concentrations of both.