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Permeability of PEGylated immunoarsonoliposomes through in vitro blood brain barrier: medulloblastoma co-culture models for brain tumor therapy

Al-Shehri, Abdulghani; Favretto, Marco E.; Ioannou, Panayiotis V.; Romero, Ignacio A.; Couraud, Pierre-Olivier; Weksler, Babette Barbash; Parker, Terry L. and Kallinteri, Paraskevi (2015). Permeability of PEGylated immunoarsonoliposomes through in vitro blood brain barrier: medulloblastoma co-culture models for brain tumor therapy. Pharmaceutical research, 32(3) pp. 1072–83.

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DOI (Digital Object Identifier) Link: https://doi.org/10.1007/s11095-014-1519-8
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Abstract

Purpose
Owing to restricted access of pharmacological agents into the brain due to blood brain barrier (BBB) there is a need: 1. to develop a more representative 3-D-co-culture model of tumor-BBB interaction to investigate drug and nanoparticle transport into the brain for diagnostic and therapeutic evaluation. 2. to address the lack of new alternative methods to animal testing according to replacement-reduction-refinement principles. In this work, in vitro BBB-medulloblastoma 3-D-co-culture models were established using immortalized human primary brain endothelial cells (hCMEC/D3).

Methods
hCMEC/D3 cells were cultured in presence and in absence of two human medulloblastoma cell lines on Transwell membranes. In vitro models were characterized for BBB formation, zonula occludens-1 expression and permeability to dextran. Transferrin receptors (Tfr) expressed on hCMEC/D3 were exploited to facilitate arsonoliposome (ARL) permeability through the BBB to the tumor by covalently attaching an antibody specific to human Tfr. The effect of anticancer ARLs on hCMEC/D3 was assessed.

Results
In vitro BBB and BBB-tumor co-culture models were established successfully. BBB permeability was affected by the presence of tumor aggregates as suggested by increased permeability of ARLs. There was a 6-fold and 8-fold increase in anti-Tfr-ARL uptake into VC312R and BBB-DAOY co-culture models, respectively, compared to plain ARLs.

Conclusion
The three-dimensional models might be appropriate models to study the transport of various drugs and nanocarriers (liposomes and immunoarsonoliposomes) through the healthy and diseased BBB. The immunoarsonoliposomes can be potentially used as anticancer agents due to good tolerance of the in vitro BBB model to their toxic effect.

Item Type: Journal Item
Copyright Holders: 2014 Springer Science+Business Media New York
ISSN: 1573-904X
Keywords: arsonolipids; blood brain barrier cancer model; cell aggregates; hCMEC/D3 cells; transferrin receptors
Academic Unit/School: Faculty of Science, Technology, Engineering and Mathematics (STEM) > Life, Health and Chemical Sciences
Faculty of Science, Technology, Engineering and Mathematics (STEM)
Interdisciplinary Research Centre: Biomedical Research Network (BRN)
Item ID: 42432
Depositing User: Ignacio A Romero
Date Deposited: 13 Apr 2015 10:45
Last Modified: 18 Nov 2016 17:57
URI: http://oro.open.ac.uk/id/eprint/42432
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