Interactions of liposomes with the reticuloendothelial system. Effects of reticuloendothelial blockade on the clearance of large unilamellar vesicles.

Large unilamellar liposomes (also called reversed phase vesicles or REVs) composed of DPPC and cholesterol are cleared from the circulation of the rat by a process which closely resembles the clearance of colloidal particles by the reticuloendothelial system. Thus, increasing the total amount of REVs administered by giving a loading dose of unlabelled REVs slows the clearance of a test dose of radioactively labelled REVs. This resembles the reticuloendothelial 'blockade' induced by large doses of colloids. Administration of other types of particles known to induce reticuloendothelial blockade, such as latex beads and xenogeneic red cells, also slows the clearance of radioactively labelled REVs. Administration of small unilamellar liposomes (SUVs) can also cause blockade of REV clearance, but the onset of blockade is delayed until a substantial fraction of the SUVs have been removed from the circulation. Blockade caused by the administration of large doses of REVs seems to result from a direct action on reticuloendothelial cells rather than from depletion of opsonic factors in the blood. Partial blockade of REV clearance produces a modest alteration of the tissue distribution of REVs, with enhanced uptake in the lungs. These results suggest that both REVs and SUVs are taken up by the reticuloendothelial system via a process which closely resembles the clearance of other types of colloids.