Serum independent liposome uptake by mouse liver

The rate of liposome clearance from blood by the reticuloendothelial system (RES), primarily the Kupffer cells of the liver, depends largely on liposome composition. Inclusion of phosphatidylserine or dicetyl phosphate into liposomes with a simple composition of phosphatidylcholine and cholesterol increases liposome clearance, while inclusion of GM1 or amphipathic poly(ethylene glycol) decreases the rate of liposome clearance. To understand the underlying mechanism by which liposome clearance is regulated by the RES, we have developed a simple liver perfusion system. Using mouse liver as a model, we demonstrated that hepatic uptake of neutral or negatively charged liposomes does not involve serum components. Liver uptake of liposomes is directly related to the surface characteristics of liposomes. Liposomes with a neutral composition of phosphatidylcholine and cholesterol exhibit relatively low liver uptake. Inclusion of PS or DCP into these liposome dramatically enhances liposome uptake by the perfused liver. Conversely, inclusion of GM1 or PEG derivatives into liposomes greatly reduces the liposome uptake by the mouse liver. In contrast to the neutral or negatively charged liposomes, serum enhances the liver uptake of positively charged liposomes. Such serum effect on liver uptake of the positively charged liposomes is likely due to liposome aggregations caused by serum proteins. Inhibition of the liver uptake for PS-containing liposomes using liposomes with different compositions suggests that liver uptake of liposomes may involve different receptors.