Distribution Within the Organs of a Reticuloendothelial System of Liposomes Containing Lipid A

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Abstract
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 (PEG-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.