Biodistribution characteristics of mannosylated, fucosylated, and galactosylated liposomes in mice
Biodistribution characteristics of mannosylated, fucosylated, and galactosylated liposomes in mice
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DOI：
10.1016/s0304-4165(00)00163-x
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发表时间：
2000-12-15
影响因子：
3
通讯作者：
Hashida, M
中科院分区：
文献类型：
--
作者：
Kawakami, S;Wong, J;Hashida, M
比较了半乳糖基（Gal）、甘露糖基（Man）和岩藻糖基（Fuc）脂质体的体内分布和药动学特征。对于糖基化脂质体的制备，将异戊烯-5-基氧基-N-（4-（（1-亚氨基-2-β-D-硫代半乳糖基乙基）氨基）烷基）甲酰胺（Gal-C4-Chol）（Kawakami等人，生物化学生物物理学Res. Commun. 252（1998）78-83）及其甘露糖基化和岩藻糖基化衍生物（分别为Man-C4-Chol和Fuc-C4-Chol）。糖基化脂质体由二硬脂酰磷脂酰胆碱（DSPC）、胆固醇（Chol）和Gal-C4-Chol（或Man-C4-Chol或Fuc-C4-Chol）组成，摩尔比为60：35：5。小鼠静脉注射后，这三种类型的[H-3]胆固醇十六烷基醚标记的糖基化脂质体迅速从循环血液中消除，并优先在肝脏中回收。相比之下，没有糖基化的DSPC/Chol（60：40）脂质体在循环血液中保留很长时间。发现实质细胞（PC）和非实质细胞（NPC）对0.5%Gal、Man和Fuc脂质体的摄取比（PC/NPC比）分别为15.1、0.6和0.2。研究了给药前糖基化蛋白和脂质体对0.5% H-3标记Gal、Man和Fuc脂质体肝脏摄取的影响，结果支持以下结论：Gal、Man和Fuc脂质体分别通过PC中的去唾液酸糖蛋白受体、NPC中的甘露糖受体和NPC中的岩藻糖受体被肝脏摄取。有趣的是，Gal脂质体在高剂量（5%）下被NPC而不是PC摄取。连同5%Gal脂质体抑制H-3标记的Fuc脂质体的肝摄取的发现，这表明以高剂量施用的Gal-脂质体也将被NPC中的岩藻糖受体摄取，其被认为充当半乳糖颗粒受体。(C)2000爱思唯尔科技有限公司。保留所有权利。
The in vivo disposition behavior and pharmacokinetic characteristics of galactosylated (Gal), mannosylated (Man) and fucosylated (Fuc) liposomes were compared in this study. For the preparation of the glycosylated liposomes, cholesten-5-yloxy-N-(4-((1-imino-2-beta -D-thiogalactosylethyl)amino)alkyl)formamide (Gal-C4-Chol) (Kawakami et al., Biochem. Biophys. Res. Commun. 252 (1998) 78-83) and its mannosylated and fucosylated derivatives (Man-C4-Chol and Fuc-C4-Chol, respectively) were synthesized. The glycosylated liposomes are composed of distearoylphosphatidylcholine (DSPC), cholesterol (Chol), and Gal-C4-Chol (or Man-C4-Chol or Fuc-C4-Chol) with the molar ratio of 60:35:5. After intravenous injection in mice, these three types of [H-3]cholesteryl hexadecyl ether-labeled glycosylated liposomes were rapidly eliminated from the circulating blood and preferentially recovered in the liver. In contrast, DSPC/Chol (60:40) liposomes without glycosylation were retained for a long time in the circulating blood. The uptake ratios by parenchymal cells (PC) and nonparenchymal cells (NPC) (PC/NPC ratios) for 0.5% Gal, Man and Fuc liposomes were found to be 15.1, 0.6 and 0.2, respectively. The effect of predosing glycosylated proteins and liposomes on the hepatic uptake of 0.5% H-3-labeled Gal, Man, and Fuc liposomes was investigated and the results support the conclusion that Gal, Man, and Fuc liposomes are taken up by the liver via asialoglycoprotein receptors in PC, mannose receptors in NPC, and fucose receptors in NPC, respectively. Interestingly, Gal liposomes were taken up by NPC rather than by PC at a high dose (5%). Together with the finding that 5% Gal liposomes inhibit the hepatic uptake of H-3-labeled Fuc liposomes, this suggests that Gal-liposomes administered at a high dose will also be taken up by fucose receptors in NPC, that are considered to act as galactose particle receptors. (C) 2000 Elsevier Science B.V. All rights reserved.