Polymersomes conjugated to 83-14 monoclonal antibodies : in vitro targeting of brain capillary endothelial cells

Dieu, Le-Ha and Wu, Dalin and Palivan, Cornelia G. and Balasubramanian, Vimalkumar and Huwyler, Jörg. (2014) Polymersomes conjugated to 83-14 monoclonal antibodies : in vitro targeting of brain capillary endothelial cells. European journal of pharmaceutics and biopharmaceutics, 88 (2). pp. 316-324.

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Official URL: http://edoc.unibas.ch/dok/A6329091

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The blood-brain barrier (BBB) remains an obstacle for many drugs to reach the brain. A strategy to cross the BBB is to modify nanocarrier systems with ligands that bind to endogenous receptors expressed at the BBB to induce receptor-mediated transport. The aim of the present study was to investigate the potential of polymersomes composed of the amphiphilic diblock copolymer poly(dimethylsiloxane)-block-poly(2-methyl-2-oxazoline), PDMS-b-PMOXA, for active targeting of brain capillary endothelial cells. We conjugated PDMS-b-PMOXA polymersomes to the anti-human insulin receptor antibody 83-14 and studied their uptake by brain capillary endothelial cells. Transmission electron micrography and light scattering measurements revealed the self-assembly of the block copolymers into 200nm vesicles after extrusion. Fluorescence correlation spectroscopy was employed to calculate the number of antibodies coupled to one polymersome. Binding and uptake of the polymersomes conjugated to 83-14mAb were studied in the human BBB in vitro model hCMEC/D3 expressing the human insulin receptor. Competitive inhibition with an excess of free 83-14mAb demonstrated the specificity of cellular binding and uptake. Our results suggest that PDMS-b-PMOXA polymersomes conjugated to 83-14mAb may be suitable nanocarriers for drug delivery to the brain.
Faculties and Departments:05 Faculty of Science > Departement Chemie > Chemie > Makromolekulare Chemie (Meier)
05 Faculty of Science > Departement Pharmazeutische Wissenschaften > Pharmazie > Pharmazeutische Technologie (Huwyler)
UniBasel Contributors:Palivan, Cornelia G and Huwyler, Jörg
Item Type:Article, refereed
Article Subtype:Research Article
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:10 Apr 2017 07:09
Deposited On:06 Feb 2015 09:58

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