Hepatocyte targeting using pegylated asialofetuin-conjugated liposomes. (April 2014)

• Record Type: Journal Article
• Authors: Detampel, Pascal; Witzigmann, Dominik; Krähenbühl, Stephan; Huwyler, Jörg
• Is Part Of: Journal of drug targeting. Volume 22:Number 3(2014)
• Page Start: 232
• Page End: 241
• Publication Date: 2014-04
• Subjects: Drug delivery systems -- Periodicals; Drug Delivery Systems; Vehicles; Drug Administration Routes; Drug Evaluation; 615.7
• DOI: 10.3109/1061186X.2013.860982
• Languages: English
• ISSNs: 1061-186X

Abstract

<abstract> <title>Abstract</title> <p> <italic>Background and purpose</italic>: 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.</p> <p> <italic>Methods</italic>: 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.</p> <p> <italic>Results: In vitro</italic>, 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 <italic>in vivo</italic> 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.</p> <p> <italic>Conclusion</italic>: 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 <italic>in vitro</italic> as well as <italic>in vivo</italic>.</p> </abstract>