Co-existence of serum-dependent and serum-independent mechanisms for liposome clearance and involvement of non-Kupffer cells in liposome uptake by mouse liver.
The effect of serum on liver uptake of liposomes with different compositions was investigated using a single-pass liver perfusion technique. Among the liposomes tested are those containing CL, PA, DPGS, PE or glycolipids such as PI, GD, GT1b and aGM1. Liposomes containing PA, CL and DPGS showed high level of liver uptake in the absence of serum. Presence of serum decreased the total liver uptake for liposomes containing CL and PA by 50% and did not affect the level of liver uptake for DPGS-containing liposomes. The presence of serum, however, significantly increased the liposome uptake by the perfused liver for PG, PE and aGM1 liposomes. Liposomes containing PI showed a minimal liver uptake regardless of serum presence. Fluorescence microscopic studies using a dual fluorescence label system in combination with Kupffer cell elimination technique showed that, in addition to the dominant role of Kupffer cells in taking up liposomes, non-Kupffer cells may also be involved in taking up CL and DCP-containing liposomes. Competition experiments using various liposome compositions indicated that liposome uptake by the liver cells may involve different receptors. Serum activity in enhancing the liver uptake for PE- and aGM1-containing liposomes can be blocked by treatment of serum with EDTA, EGTA/Mg2+ and high temperature (56 degrees C), suggesting the involvement of complement system. Results from this study support the conclusion that blood clearance of liposomes by the liver involves two independent mechanisms, one requires serum opsonins and the other does not.
Department of Pharmaceutical Sciences, School of Pharmacy, University of Pittsburgh, PA 15261, USA.
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D000818:Animals; D001769:Blood; D002784:Cholesterol / Q000493:pharmacokinetics; D004337:Drug Carriers; D005732:Gangliosides / Q000493:pharmacokinetics; D006017:Glycolipids / Q000493:pharmacokinetics; D007728:Kupffer Cells / Q000378:metabolism*; D008055:Lipids / Q000493:pharmacokinetics*; D008081:Liposomes; D008099:Liver / Q000378:metabolism*; D051379:Mice; D010477:Perfusion / Q000379:methods; D010712:Phosphatidic Acids / Q000493:pharmacokinetics; D013329:Structure-Activity Relationship
D004337:Drug Carriers; D005732:Gangliosides; D006017:Glycolipids; D008055:Lipids; D008081:Liposomes; D010712:Phosphatidic Acids; D002784:Cholesterol