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Hepatocyte targeting using pegylated asialofetuin-conjugated liposomes

Detampel, Pascal and Witzigmann, Dominik and Krähenbühl, Stephan and Huwyler, Jörg. (2014) Hepatocyte targeting using pegylated asialofetuin-conjugated liposomes. Journal of drug targeting, Vol. 22, No. 3. pp. 232-241.

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Official URL: http://edoc.unibas.ch/dok/A6211980

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Abstract

Background and purpose: 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. Conclusion: 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.
Faculties and Departments:03 Faculty of Medicine > Bereich Medizinische Fächer (Klinik) > Klinische Pharmakologie > Klinische Pharmakologie (Krähenbühl)
03 Faculty of Medicine > Departement Klinische Forschung > Bereich Medizinische Fächer (Klinik) > Klinische Pharmakologie > Klinische Pharmakologie (Krähenbühl)
05 Faculty of Science > Departement Pharmazeutische Wissenschaften > Pharmazie > Pharmakologie (Krähenbühl)
05 Faculty of Science > Departement Pharmazeutische Wissenschaften > Pharmazie > Pharmazeutische Technologie (Huwyler)
UniBasel Contributors:Detampel, Pascal and Huwyler, Jörg and Witzigmann, Dominik and Krähenbühl, Stephan
Item Type:Article, refereed
Article Subtype:Research Article
Bibsysno:Link to catalogue
Publisher:Taylor & Francis
ISSN:1061-186X
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:06 Mar 2015 07:44
Deposited On:20 Jun 2014 07:56

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