Different intrahepatic distribution of phosphatidylglycerol and phosphatidylserine liposomes in the rat
Different intrahepatic distribution of phosphatidylglycerol and phosphatidylserine liposomes in the rat
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DOI：
10.1002/hep.510260223
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发表时间：
1997-08-01
期刊：
影响因子：
13.5
通讯作者：
Scherphof, GL
中科院分区：
文献类型：
--
作者：
Daemen, T;Velinova, M;Scherphof, GL
将直径为200 ~ 400nm的含有磷脂酰丝氨酸（PS）或磷脂酰甘油（PG）的脂质体静脉注射到大鼠体内，注射2小时后，PS脂质体在肝脏中发现了注射剂量的T5%，在脾脏中只发现了10%，而PG脂质体在肝脏中发现了35%，在脾脏中发现了高达40%。细胞分离实验揭示了两种脂质体制剂在肝内分布的显著差异：PS脂质体分布在库普弗细胞和肝细胞中，尽管它们的大小（200-400 nm）超过了内皮细胞的孔径（平均150 Mt），而PG脂质体只被库普弗细胞吸收，而肝细胞完全不吸收。双标记研究使用脂质体，其中脂质部分用[H-3]胆固醇酰醚（[H-3]CE）放射性标记，水相用[C-14]蔗糖标记。表明脂质体被完整地吸收。这些观察结果通过电子显微镜通过测定脂质体包裹的胶体金颗粒在肝脏和脾脏薄片的原位定位得到证实。器官分布的差异归因于两种脂质体表面的调理模式的差异。对于肝内分布的差异，我们提供以下两种解释：利用血细胞介导的强制筛分概念和ps特异性药理作用对开窗尺寸的指示（HEPATOLOGY 1997; 26:16 -423）。
Liposomes with diameters of 200 to 400 nm containing phosphatidylserine (PS) or phosphatidylglycerol (PG) were injected intravenously into rats, Two hours after injection, T5% of the injected dose of PS liposomes was found in the liver and only 10% found in the spleen, while 35% of the PG liposomes was found in the liver and as much as 40% was found in the spleen. Cell-isolation experiments revealed the following remarkable difference in the intrahepatic distribution between the two liposome formulations: the PS liposomes distributed in about equal amounts to Kupffer cells and hepatocytes, despite their size (200-400 nm) exceeding that of the endothelial fenestrae (average 150 Mt), whereas the PG liposomes were only taken up by the Kupffer cells and not at all by the hepatocytes, Double-label studies, using liposomes in which the lipid-moiety was radio labeled with [H-3]cholesteryloleylether ([H-3]CE) and the water phase with [C-14]sucrose, showed that the liposomes were taken up as intact particles. These observations were confirmed through electron microscopy by determining the in situ localization of liposome-encapsulated colloidal gold particles in thin sections of liver and spleen. The differences in organ distribution are ascribed to differences in opsonization patterns of the two liposomal surfaces. For the difference in intrahepatic distribution, we offer the following two explanations: the exploitation of the blood cell-mediated forced sieving concept and the indication of a PS-specific pharmacological effect on the dimensions of the fenestrations (HEPATOLOGY 1997;26:416-423.).