酸性成纤维细胞生长因子阳离子脂质体在大鼠体内的药动学

Pharmacokinetics of aFGF Cationic Liposomes in Rats

采用pH梯度法制备了酸性成纤维细胞生长因子(aFGF)阳离子脂质体,建立了生物素-亲和素放大酶联免疫吸附测定(BA-ELISA)法检测大鼠血清中的药物浓度。结果显示,血清中的aFGF浓度在31.2~500 pg/ml范围内线性关系良好,回收率大于97%,日内、日间RSD<10%。大鼠分别尾静脉注射不同剂量(20、50和100μg/kg)的aFGF阳离子脂质体和aFGF溶液,用以考察制品在大鼠体内的药动学行为。结果显示,低、中、高浓度的aFGF阳离子脂质体与aFGF溶液相比,阳离子脂质体组的消除半衰期(t1/2)和平均滞留时间(MRT)均显著延长(P<0.05);阳离子脂质体组的药-时曲线下面积(AUC)呈现出剂量依赖性增长,并且高剂量组的AUC与高浓度aFGF溶液组相比有极显著差异(P<0.01)。本研究结果表明,aFGF阳离子脂质体延长了aFGF的体内存在时间,有效提高了aFGF的生物利用度。

The cationic liposomes loaded with acidic fibroblast growth factor(aFGF)were prepared by pH gradient method,and a biotin-avidin amplified enzyme-linked immunosorbent assay(BA-ELISA)method was established to determine the concentration of aFGF in rat serum.This method was linear in the concentration range of 31.2-500 pg/ml,and had high recoveries(>97.0%)with intra-and inter-day relative standard deviation(RSD)below 10%.The pharmacokinetic behaviors of the aFGF in SD rats were investigated by tail vein injection of different dosages(20,50 and 100μg/kg)of the cationic liposomes or the solutions.The results showed that the elimination half-life(t1/2)and mean residence time(MRT)of aFGF in low-,medium-and high-dosage groups of cationic liposomes were significantly higher than those in aFGF solution groups(P<0.05).The area under the drug concentration-time curve(AUC)of cationic liposome groups showed a dose-dependent increase,and the AUC value in high-dosage group of liposomes was extremely higher than that in high-dosage group of solution(P<0.01).These results indicated that aFGF cationic liposomes could prolong the duration of aFGF in the body,and effectively improve its bioavailability.