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.