Distribution within the organs of a reticuloendothelial system of liposomes containing lipid A.
Lipid A was incorporated into egg phosphatidylcholine (PC)/cholesterol liposomes which were then tested in mice in order to investigate the effect of lipid A on in vivo biodistribution of liposomes. Addition of lipid A up to 3.2 mol% decreased hepatic uptake and slightly increased splenic uptake of liposomes. When more than 3.2 mol% lipid A incorporated into liposomes, hepatic uptake increased with lipid A concentration. Liposomes containing 25 mol% lipid A were rapidly cleared from circulation and taken up mainly by the liver. Ganglioside GM1 or N-monomethoxypoly(ethyleneglycol)-phosphatidylethanolamine (PGE-PE), which is known to prolong the half life of circulating liposomes, was included in liposomes along with lipid A. Lipid A antagonized the effect of GM1 more effectively than that of PEG-PE. This may be due to the different mechanisms of action exerted by GM1 and PEG-PE in liposome circulation. Hepatic uptake of liposomes containing lipid A increased with vesicle size. However, the unique splenic accumulation of large PEG-PE liposomes was only slightly affected by inclusion of a small amount of lipid A (< 7 mol%). These liposomes might be useful for intravenous delivery of antigen to the spleen for increased immune response.
Park
Y S
YS
Department of Biochemistry, University of Tennessee, Knoxville 37996-0840.
Huang
L
L
D000818:Animals; D004337:Drug Carriers; D005260:Female; D005677:G(M1) Ganglioside / Q000494:pharmacology; D007205:Indium Radioisotopes; D008050:Lipid A / Q000008:administration & dosage / Q000493:pharmacokinetics*; D008081:Liposomes; D008099:Liver / Q000378:metabolism; D051379:Mice; D008813:Mice, Inbred ICR; D012157:Mononuclear Phagocyte System / Q000378:metabolism*; D010316:Particle Size; D011092:Polyethylene Glycols / Q000494:pharmacology; D013154:Spleen / Q000378:metabolism; D014018:Tissue Distribution
D004337:Drug Carriers; D007205:Indium Radioisotopes; D008050:Lipid A; D008081:Liposomes; D005677:G(M1) Ganglioside; D011092:Polyethylene Glycols