DIFFERENT INTRAHEPATIC DISTRIBUTION OF PHOSPHATIDYLGLYCEROL AND PHOSPHATIDYLSERINE LIPOSOMES IN THE RAT

Liposomes with diameters of 200 to 400 nm containing phosphatidylserin e (PS) or phosphatidylglycerol (PG) were injected intravenously into r ats, Two hours after injection, T5% of the injected dose of PS liposom es was found in tile 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 fou nd in the spleen. Cell-isolation experiments revealed the following re markable difference in the intrahepatic distribution between the two l iposome formulations: the PS liposomes distributed in about equal amou nts 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 al l by the hepatocytes, Double-label studies, using liposomes in which t he lipid-moiety was radio labeled with [H-3]cholesteryloleylether ([H- 3]CE) and the water phase with [C-14]sucrose, showed that the liposome s were taken up as intact particles. These observations were confirmed through electron microscopy by determining the in situ localization o f liposome-encapsulated colloidal gold particles in thin sections of l iver and spleen. The differences in organ distribution are ascribed to differences in opsonization patterns of the two liposomal surfaces. F or the difference in intrahepatic distribution, we offer tile followin g two explanations: the exploitation of the blood cell-mediated forced sieving concept and the indication of a PS-specific pharmacological e ffect on the dimensions of the fenestrations (HEPATOLOGY 1997;26:416-4 23.).