Abstract
In this contribution we summarize our observations over a period of nearly two decennia on the role of hepatocytes in the hepatic clearance of intravenously administered liposomes. We demonstrate that, although size is an important parameter, it is not decisive in determining access of liposomes to the hepatocytes. Also lipid composition is an important parameter, including charge, rigidity and headgroup composition. The role of the fenestrated sinusoidal endothelial cells in accessibility is discussed as well as the involvement of opsonizing plasma proteins such as apolipoprotein E. Our observations led us to hypothesize at least four different mechanisms of interaction of liposomes with hepatocytes.