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Uptake and permeability studies of BBB-targeting immunoliposomes using the hCMEC/D3 cell line

Markoutsa, Eleni; Pampalakis, Georgios; Niarakis, Anna; Romero, Ignacio A.; Weksler, Babette; Couraud, Pierre-Olivier and Antimisiaris, Sophia G. (2011). Uptake and permeability studies of BBB-targeting immunoliposomes using the hCMEC/D3 cell line. European Journal of Pharmaceutics and Biopharmaceutics, 77(2) pp. 265–274.

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DOI (Digital Object Identifier) Link: http://dx.doi.org/10.1016/j.ejpb.2010.11.015
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Abstract

The targeting potential of OX-26-decorated immunoliposomes was investigated, using the human brain endothelial cell line hCMEC/D3 as a model of the blood-brain barrier (BBB). Immuno-nanoliposomes were prepared by the biotin/streptavidin ligation strategy, and their uptake by hCMEC/D3 cells and permeability through cell monolayers was studied. In order to elucidate the mechanisms of uptake, pH-sensitive fluorescence signal of HPTS was used, while transport was measured using double labeled immunoliposomes (with aqueous and lipid membrane fluorescent tags). PEGylated and non-specific-IgG-decorated liposomes were studied under identical conditions, as controls. CHO-K1 cells (which do not overexpress the transferrin receptor) were studied in some cases for comparative purposes.

Experimental results reveal that hCMEC/D3 cells are good models for in vitro screening of BBB-targeting nanoparticulate drug delivery systems. Uptake and transcytosis of immunoliposome-associated dyes by cell monolayers was substantially higher compared to those of control liposomes. HPTS-entrapping OX-26-immunoliposome uptake indicated lysosomal localization and receptor-mediated mechanism. The ratio of aqueous/lipid label transport is affected by pre-incubation with antibody, or use of high lipid doses, suggesting that vesicles are transported intact after lysosome saturation. Co-decoration with a second ligand slightly decreases OX-26-decorated vesicle uptake, but not transcytosis, proving that the biotin–streptavidin technique can be applied for the generation of dual-targeting nanoliposomes.

Item Type: Journal Article
Copyright Holders: 2010 Elsevier B.V.
ISSN: 0939-6411
Keywords: dual targeting; blood-brain barrier; transcytosis; immunoliposomes; transferrin; OX-26 antibody
Academic Unit/Department: Science > Life, Health and Chemical Sciences
Interdisciplinary Research Centre: Biomedical Research Network (BRN)
Item ID: 25918
Depositing User: Astrid Peterkin
Date Deposited: 06 Jan 2011 11:40
Last Modified: 13 Mar 2014 17:34
URI: http://oro.open.ac.uk/id/eprint/25918
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