Preferential uptake of lactosylceramide-bearing dipalmitoylphosphatidylcholine-liposomes into liver: role of membrane fluidity.

The effect of the membrane fluidity of lactosylceramide (LacCer)-bearing liposomes on their liver uptake was investigated in rats. Liposomes consisting of phosphatidylcholine (PC): cholesterol:dicetylphosphate:LacCer (7:2:1:1, molar ratio) were prepared with various fluidities using dipalmitoylphosphatidylcholine (DPPC), dimyristoylphosphatidylcholine (DMPC) and egg PC. These liposomes were all equally stable in serum and were small enough to pass freely through the fenestrae and be taken up easily by liver cells. The LacCer modification of DPPC-liposomes markedly facilitated blood clearance, whereas no enhancing effect of LacCer was observed with egg PC- and DMPC-liposomes. Tissue distribution studies showed the preferential liver uptake of LacCer-bearing DPPC-liposomes, which was largely compatible with the rapid clearance induced by the LacCer modification. In addition, electron spin resonance (ESR) spectroscopic analysis revealed that the LacCer modification of DPPC-liposomes significantly enhanced the order parameter S, indicating that LacCer-bearing DPPC-liposomes were the most rigid of those used in this study. These observations suggest that the membrane fluidity of liposomes in vivo is a crucial factor for their preferential liver uptake.