Liposome clearance from blood: different animal species have different mechanisms

The kinetics of blood clearance and the mechanisms of liposome uptake by the reticuloendothelial system (RES) were compared in two animal species (mice and rats). By employing an in situ liver perfusion technique with selected liposome compositions (PC/Chol, PC/Cho/PS, PC/Chol/GM1 and PC/Chol/PEG5000-PE), we demonstrated that liposomes with same lipid composition exhibited different blood circulation half-lives in different animal species. Although liver is the major organ responsible for the clearance of liposomes from blood in both animal species, the specific mechanisms differ. In mice, liposome uptake by the liver did not involve specific serum opsonins. In contrast, liposome uptake by the rat liver was strongly dependent on serum opsonins. Further, the activity of serum opsonins for a given liposome composition differed among animal species. Human serum exhibited higher opsonin activities for PC/Chol and PC/Chol/GM1 liposomes than bovine sera, while rat serum displayed a high opsonizing activity for GM1 liposomes and none for liposomes composed of PC and Chol. The opsonin activity of human serum could be removed or decreased by treatment with EGTA/Mg2+, EDTA or cobra venom factor, suggesting that the activity is likely due to complement components. It is likely that C3 of the human complement system plays an important role in mediating the uptake of liposomes by the liver.