超氧化物歧化酶脂质体在大鼠体内的药代动力学和组织分布

Pharmacokinetics and distribution of superoxide dismutase liposomes in rats

目的 考察 3种超氧化物歧化酶(SOD)脂质体静脉给药后在大鼠体内的药代动力学和组织分布。方法用反相蒸发法制备SOD脂质体,采用黄嘌呤氧化酶法检测SOD活力,静脉注射给药后,测定大鼠血中SOD含量变化和不同组织中SOD含量变化。结果 在血浆中,SOD水溶液、SOD普通脂质体、用DSPE- PEG2000修饰的SOD脂质体、用Tween80修饰的SOD脂质体的半衰期分别为 0 .25, 0 .34, 0. 66和 0 .41h;AUC分别为 12. 48, 24 .66, 41. 16和33. 02μg·h·mL-1。与普通脂质体比较,经过DSPE- PEG和Tween80修饰后的脂质体,使肝、脾中SOD的含量有不同程度的降低,脑中含量有所提高。结论 3种SOD脂质体均可不同程度地延长SOD的血浆半衰期,并以用DSPE PEG2000修饰的SOD脂质体效果最好。与普通脂质体相比,用Tween80修饰的SOD脂质体可以提高进入脑中的SOD量,用DSPE PEG2000修饰的SOD脂质体可以减少肝脾对SOD的摄取。

Aim To evaluate the effects of surfactants on the pharmacokinetics and distribution in rats after intravenous administration of SOD liposomes. Methods The liposomes were prepared by reverse phase evaporation method. The activity of SOD was assayed by method of xanthine oxidase. Results The T 1/2 of SOD solution, common SOD liposome, SOD liposomes modified by DSPE-PEG2000 and Tween 80 were 0.25, 0.34, 0.66 and 0.41 h, respectively; AUC were 12.48, 24.66, 41.16 and 33.02 μg·h·mL-1, respectively. Compared with the common liposome, the liposomes modified by DSPE-PEG and Tween 80 decreased the content of SOD in liver and spleen, but increased in brain. Conclusion The three kinds of liposomes could increase T 1/2 and AUC in some extent, especially in PEG-L group. Tween-L could increase the SOD content in brain, and PEG-L could decrease the SOD content in the liver and spleen compared with the common liposome.