リポソーム膜中のコレステロール含量が及ぼす補体第３成分（Ｃ３）の結合と体内動態への影響

Abstract

In this study we analyzed the binding ability of complement component 3 (C3) associated with liposomes after incubation in rat serum in order to determine the effect of cholesterol content of liposomes on the complement system liposomes interactions and the fate of liposomes in vivo. Liposomes having different cholesterol content showed no difference in clearances from blood circulation, while in both hepatic and renal clearances the liposomes showed marked difference. The hepatic clearance increased with increasing cholesterol content and the renal clearance decreased with increasing cholesterol content. Further, it appeared that those liposomes had different C3 binding potentials : cholesterol-rich (44 mol%) liposomes had higher affinity for C3 than cholesterol-poor (22 mol%) liposomes. Interestingly, there was a good correlation between the C3 binding ability and hepatic clearance of liposomes, while there was an inverse correlation between the C3 binding ability and renal clearance of liposomes. These results suggested that the extent of interaction of liposomes with complement system directly related to the distribution of liposomes in liver, leading to a possibility that the liposomes having high affinity for C3 are phagocytosed by Kuppfer cells via complement receptors. Release of encapsulated carboxy fluorescein from liposomes was inhibited in heat-treated rat serum, less done in EDTA-treated one. This finding indicated that degradation of liposomes in in vivo or in vitro was attributed to a heat-labile serum component, but not complement system. We clarified in this study that the complement-liposome interactions play a critical role on the hepatic uptake of liposomes, but not on the degradation of liposomes in blood circulation.