The role of hepatocytes in the clearance of liposomes from the blood circulation.
In this chapter we summarize literature and describe in more detail our own observations over a period of nearly two decennia on the role of hepatocytes in the hepatic clearance of intravenously administered liposomes. Evidence is presented indicating 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 determining liposome accessibility of hepatocytes is discussed as well as the involvement of opsonizing plasma proteins such as apolipoprotein E. Our observations led us to postulate the existence of at least four different mechanisms of interaction of liposomes with hepatocytes, i.e. an endocytic and a non-endocytic one for both neutral and negatively charged vesicles
Scherphof
G L
GL
Department of Physiological Chemistry, Groningen University Institute for Drug Exploration, University of Groningen, A. Deusinglaan 1, 9713 AV, The, Groningen, Netherlands. g.l.scherphof@med.rug.nl
Kamps
J A
JA
D001057:Apolipoproteins E / Q000502:physiology; D001646:Bile / Q000378:metabolism; D002452:Cell Count; D048429:Cell Size; D004705:Endocytosis; D004730:Endothelium, Vascular / Q000502:physiology; D022781:Hepatocytes / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D008081:Liposomes; D008657:Metabolic Clearance Rate; D009895:Opsonin Proteins / Q000502:physiology; D011956:Receptors, Cell Surface; D018110:Receptors, Lipoprotein
D001057:Apolipoproteins E; D008081:Liposomes; D009895:Opsonin Proteins; D011956:Receptors, Cell Surface; D018110:Receptors, Lipoprotein; C039707:galactose receptor