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)-5-125 I-N-(1-ethyl-2-pyrrolidinyl) methyl-4-amine-2-methoxy-benzamide (125 I-AIBZM ) as an imaging agent. Both 125 I-AIBZM-nanoliposome (125 I-AIBZML) and 125I-AIBZM-lactoferrin-nanoliposome (125 I-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.%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).
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