具有脑靶向功能的^125I-AIBZM纳米脂质体  

^(125)I-AIBZM Nanoliposomes Targeting Brain as Imaging Agents

作　　者：李光慧[1] 沈海星[1] 钱隽[1] 司展[1] 朱建华[1] 

机构地区：[1]复旦大学药学院放射药学教研室,教育部和全军智能化递药重点实验室,上海201203

出　　处：《高等学校化学学报》2011年第6期1295-1300,共6页Chemical Journal of Chinese Universities

基　　金：国家“九七三”计划项目(批准号:2007CB935800)资助

摘　　要：将苯甲酰胺类衍生物125I-(S)-5-碘-N-(1-乙基-2-吡咯烷基)甲基-4-氨基-2-甲氧基苯酰胺(125I-AIBZM)包载于具有脑靶向功能的纳米脂质体载药系统中,以提高125I-AIBZM的入脑量.采用硫酸铵梯度主动载药法制备了125I-AIBZM-脂质体(125I-AIBZM-L)和125I-AIBZM-Lf-脂质体(125I-AIBZM-Lf-L),脂质体形状规则,分布均匀,粒径在100 nm左右,两种脂质体的125I-AIBZM包封率分别为39%和35%.包载荧光素DIR的DIR-脂质体(DIR-L)和DIR-Lf-脂质体(DIR-Lf-L)的小鼠荧光活体成像研究显示,DIR-Lf-L具有明显的脑靶向性,证实了乳铁蛋白(Lf)介导脑靶向的功能.药动力学实验表明,125I-AIBZM-L与125I-AIBZM-Lf-L在大鼠体内的血循环时间比125I-AIBZM明显延长,各时相125I-AIBZM-Lf-L的入脑量显著高于125I-AIBZM-L(P<0.01),而125I-AIBZM-L的入脑量又显著高于125I-AIBZM(P<0.01).The aim of this study is to develop a blood brain barrier permeable nano-liposome drug delivery system that significantly up-regulates the brain uptake of（S）-5-^125I-N-（1-ethyl-2-pyrrolidinyl）methyl-4-amine-2-methoxy-benzamide（^125I-AIBZM） as an imaging agent.Both 125I-AIBZM-nanoliposome（^125I-AIBZM-L） and ^125I-AIBZM-lactoferrin-nanoliposome（^125I-AIBZM-Lf-L） were prepared by the ammonium sulfate gradient method with a small particle size（ca.100 nm） and a narrow size distribution pattern.The encapsulation efficiencies of ^125I-AIBZM-L and 125I-AIBZM-Lf-L were measured as 39% and 35%,respectively.In vivo fluorescence imaging results showed that DIR-Lf-L was successfully delivered drug into the brain.The pharmacokinetic experiments in rats indicated that the blood circulation times of 125I-AIBZM-L and ^125I-AIBZM-Lf-L were substantially longer than that of small molecular 125I-AIBZM.Amount of intracerebral ^125I-AIBZM delivered by ^125I-AIBZM-L was significantly lower than that of ^125I-AIBZM-Lf-L（P〈0.01） but remarkably higher than that of ^125I-AIBZM（P〈0.01）.In conclusion,^125I-AIBZM-Lf-L nano-liposome drug delivery system can increase the brain uptake of imaging agent 125I-AIBZM.

关 键 词：125I 多巴胺D2受体 乳铁蛋白 脂质体 荧光活体成像 

分 类 号：O628.5[理学—有机化学]