title: Hepatocyte targeting using pegylated asialofetuin-conjugated liposomes.
abstract: OBJECTIVE
  The hepatocyte asialoglycoprotein receptor mediates uptake of desiaylated glycoproteins by receptor-mediated endocytosis. This work explores a hepatocyte-specific targeting strategy using asialofetuin (AF) covalently coupled to pegylated liposomes.
  
  
  METHODS
  AF was conjugated to the distal end of polyethylene glycol-functionalized phospholipids. Chemical modification of AF did not interfere with its receptor interaction. AF-liposomes had a size of less than 130 nm, were judged to be monodisperse and were labelled with fluorescent organic dyes or loaded with quantum dots.
  
  
  RESULTS
  In vitro, binding and cellular uptake of fluorescent AF-liposomes by HepG2 hepatocellular carcinoma cells were reduced at low temperature and could be competitively inhibited by an excess of unbound AF. Hepatocyte-specific targeting and internalization of AF-liposomes in vivo was confirmed in the rat and could be competitively inhibited by co-injection of unbound AF. In contrast, non-pegylated liposomes accumulated in cells of the reticuloendothelial system such as hepatic Kupffer cells and spleen after intravenous administration.
  
  
  CONCLUSIONS
  We conclude that the use of AF-conjugated, pegylated liposomes is a promising strategy to avoid the reticuloendothelial system and specifically target hepatocytes via the asialoglycoprotein receptor in vitro as well as in vivo.
authors: a Department of Pharmaceutical Sciences, Division of Pharmaceutical Technology, University of Basel Basel Switzerland.
authors: Pascal
authors: P
authors: Detampel
authors: a Department of Pharmaceutical Sciences, Division of Pharmaceutical Technology, University of Basel Basel Switzerland.
authors: Dominik
authors: D
authors: Witzigmann
authors: b Division of Clinical Pharmacology and Toxicology, University Hospital Basel Switzerland.
authors: Stephan
authors: S
authors: Krähenbühl
authors: a Department of Pharmaceutical Sciences, Division of Pharmaceutical Technology, University of Basel Basel Switzerland.
authors: Jörg
authors: J
authors: Huwyler
keywords: Asialofetuin; HepG2; asialoglycoprotein receptor; hepatocyte; liver targeting; quantum dots