【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).更多还原

【Abstract】 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.更多还原