不同类型长循环脂质体在动物体内的分布和药代动力学研究  

Pharmacokinetics and Tissue Distribution of Long Circulating Liposomes in Rabbits and Mice

作　　者：马超[1,2] 匡安仁[1] 

机构地区：[1]四川大学华西医院核医学科,成都610041 [2]青岛大学医学院附属医院核医学科

出　　处：《四川大学学报（医学版）》2011年第2期249-251,268,共4页Journal of Sichuan University(Medical Sciences)

基　　金：国家自然科学基金(批准号30700185)资助

摘　　要：目的研究不同类型长循环脂质体在动物体内的药代动力学和组织分布。方法昆明大白兔和小鼠静脉内注射阴离子长循环脂质体(NA)、阳离子长循环脂质体(PA)和中性长循环脂质体(A-D),以及普通脂质体(CA)和游离125I-反义寡核苷酸(ASON)(FA),不同时间点分别采集血样本和组织器官,测量其放射性,用3p87软件拟合曲线方程,获得药代动力学参数和小鼠体内组织分布。结果 NA、PA、A-D、CA和FA在大白兔体内的药代动力学符合二室模型。NA能明显延长125I-bcl-2/bcl-xl ASON在动物体内的半衰期(T1/2α、T1/2β),增大血药浓度-时间曲线下面积,降低肝脏等网状内皮系统的摄取。4种脂质体和FA在小鼠肝、脾、肾分布较多,脑、肌肉和骨骼内的放射性分布较少(<1%ID/g)。在静脉注射后4 h,与CA比较,小鼠肝脏摄取NA减少30%。脾脏摄取4种脂质体的差异无统计学意义(P>0.05)。结论 NA是介导放射反义治疗的理想载体。Objective To investigate the pharmacokinetic profiles and tissue distribution of long circulating liposome formulations-anionic,cationic,and neutral long circulating liposomes（NA,PA,A-D） in rabbits and mice.Methods Conventional liposomes（CA） encapsulated with 125I-bcl-2/bcl-xl ASON and free 125I-bcl-2/bcl-xl ASON （FA） were intravenously administered to rabbits and mice.The blood samples from rabbits and organs from mice were collected,respectively.The radioactivity of the blood and tissues samples were measured.Results The clearance of the four kinds of liposomes and FA exhibited bicompartmental behaviors.Compared with others,NA demonstrated favourable pharmacokinetic properties characterized with enhancement of T1/2α and T1/2β,increased area under concentration-time curve,and decreased liver uptake.Higher uptake in the liver,spleen and kidney of mice and lower uptake in the brain,muscle,and bone of mice were observed shortly after intravenous injection of the four different kinds of liposomes and FA.A 30 % decrease in uptake of NA was found in the liver of mice four hours after intravenous injection compared with the uptake of CA.No significant differences were found in the uptake of the four kinds of liposomes in the pleen of mice（P〉0.05）.Conclusion NA is promising as a carrier for radio-antisense therapy.

关 键 词：长循环脂质体 放射性碘 反义寡核苷酸 药代动力学 

分 类 号：R96[医药卫生—药理学]