泊洛沙姆188修饰的蜂毒素脂质体在大鼠体内的药动学

Pharmacokinetics of melittin liposomes modified with poloxamer188 in rats

目的:考察泊洛沙姆188(poloxamer188)修饰的蜂毒素脂质体在大鼠体内的药动学。方法:大鼠尾静脉分别注射蜂毒素溶液(MLT-I)、2%及5%Poloxamer188修饰的蜂毒素脂质体(MLT-LIPO-2%和MLT-LIPO-5%),采用酶联免疫吸附(ELISA)方法测定大鼠体内的蜂毒素。结果:采用Kinetica4.4统计软件,经统计矩拟合后,与MLT-I相比,MLT-LIPO-2%和MLT-LIPO-5%在大鼠体内的药动学行为发生显著变化,清除率(CL)分别为溶液组的48.3%及33.2%;血药浓度-时间曲线下面积(AUC)分别为溶液组的2.01倍及2.82倍;平均滞留时间(MRT)分别为溶液组的1.80倍及2.18倍。结论:经poloxamer188修饰后的脂质体显著延长了药物在大鼠体内的驻留时间,提高了药物的生物利用度,且与膜修饰剂的用量有一定的正相关性。

OBJECTIVE To evaluate the pharmacokineties of melittin （MLT） liposomes （LIPO） modified with poloxamer188 in rats. METHODS Following administration of MLT solution （MLT-I）,MLT liposome with 2% and 5% poloxamer188（MLT LIPO-2% and MLT-LIPO-5%） to rats via tail veins, respectively, the concentration of MLT in vivo was determined by ELISA. RESULTS The PK studies showed that behavior of MLT LIPO-2% and MLT-LIPO-5% in vivo changed significantly compared to MLT I. The gained data fitted the two compartment model, the CL was 48. 3% and 33.2% respectively, AUC was 2.01 and 2.82 fold, and the MRT was 1.80 and 2. 18 fold respectively comparable to those of MLT-I. CONCLUSION All above indicates that MLT LIPO modified by poloxamer188 exhibits longer circulation time in vivo and improved bioavailability, which is related with the amount of poloxamer188.