摘要
We investigated the bio-distributions of [125 I]Spiro-I formulated in sterically stabilized liposomes （SSL） or targeted liposomes （SSTL） in mice,especially their brain uptake.The [125 I]Spiro-I liposomes were prepared by film-ultrasound dispersion method.Cereport （RMP-7） was covalently conjugated with DSPE-PEG,which was attached to the surface of SSL to form SSTL.The encapsulation efficiencies （ee%） of [125 I]Spiro-I-SSL and [125 I]Spiro-I-SSTL were 97.47%±4.01% and 93.02%±2.98%,respectively.The average particle sizes were （66.47±0.76） nm and （71.40±0.45） nm,respectively.After intravenous administration,[125 I]Spiro-I was quickly eliminated from blood.SSL could prolong the retention time of [125 I]Spiro-I in blood and SSTL improved its brain uptake.The AUC of [125 I]Spiro-I-SSTL in brain was increased by 1.52 times as compared to [125 I]Spiro-I,indicating that SSTL could be used for the formulation of [125 I]Spiro-I for the imaging of central nervous system （CNS）.
研究[125 I]Spiro-I经长循环脂质体(SSL)和脑靶向脂质体(SSTL)包载后的组织分布, 尤其考察其脑摄入。采用薄膜超声分散法制备[125 I]Spiro-I脂质体, RMP-7通过共价键连在DSPE-PEG上进一步形成靶向脂质体。[125 I]Spiro-I-SSL及 SSTL的包封率分别为97.47%±4.01%, 93.02%±2.98%, 粒径分别为(66.47±0.76) nm, (71.40±0.45) nm。给药后, [125 I]Spiro-I迅速从血液中清除, 长循环组延长了药物在血液中的保留时间, RMP-7提高了[125 I]Spiro-I的脑摄取量。[125 I]Spiro-I-SSTL组的AUC较游离药物组提高了1.52倍。SSTL有望拓展显像剂在中枢神经系统的应用。
基金
National Basic Research Program of China (973 Program, Grant No. 2009CB930300)
National Natural Science Foundation of China (Grant No.20501004 and 20871021)
