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Targeting of daunomycin using biotinylated immunoliposomes: Pharmacokinetics, tissue distribution and in vitro pharmacological effects

Schnyder, Anita and Krähenbühl, Stephan and Drewe, Jürgen and Huwyler, Jörg. (2005) Targeting of daunomycin using biotinylated immunoliposomes: Pharmacokinetics, tissue distribution and in vitro pharmacological effects. Journal of Drug Targeting, 13 (5). pp. 325-335.

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Official URL: http://edoc.unibas.ch/54629/

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Abstract

Biotinylated immunoliposomes were prepared by a non-covalent (biotin-streptavidin) coupling procedure and conjugated to the OX26 monoclonal antibody directed against the rat transferrin receptor. In vitro, these biotinylated immunoliposomes were used to by-pass P-glycoprotein in multidrug-resistant RBE4 brain capillary endothelial cells and thereby to achieve 2- to 3-fold higher intracellular accumulation of liposomal daunomycin as compared to free drug. The extent of cellular uptake of liposomal daunomycin was dose- and time-dependent, was inhibited by competition with unbound OX26 and was associated with a pharmacological (i.e. cytotoxic) effect. Cytotoxic effects of liposomal formulations of daunomycin, in contrast to the free drug, were apparent only after prolonged incubation periods being indicative of a slow intracellular unpacking and release of liposomal daunomycin. Pharmacokinetics and tissue distribution studies in the rat revealed brain accumulation of daunomycin in OX26-immunoliposomes to higher levels as compared to brain uptake of free daunomycin, or daunomycin incorporated within pegylated liposomes or within unspecific IgG(2a) isotype control immunoliposomes. Such OX26-mediated effects were not observed in other tissues such as spleen, liver, muscle or kidney.
Faculties and Departments:05 Faculty of Science > Departement Pharmazeutische Wissenschaften > Pharmazie > Pharmazeutische Technologie (Huwyler)
UniBasel Contributors:Huwyler, Jörg and Krähenbühl, Stephan and Drewe, Jürgen
Item Type:Article, refereed
Article Subtype:Research Article
Publisher:Taylor & Francis
ISSN:1061-186X
e-ISSN:1029-2330
Note:Publication type according to Uni Basel Research Database: Journal article
Identification Number:
Last Modified:23 Nov 2017 08:12
Deposited On:23 Nov 2017 08:12

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