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Functionalized Solid-Sphere PEG-b-PCL Nanoparticles to Target Brain Capillary Endothelial Cells In Vitro

Grossen, Philip and Québatte, Gabriela and Witzigmann, Dominik and Prescianotto-Baschong, Cristina and Dieu, Le-Ha and Huwyler, Jörg. (2016) Functionalized Solid-Sphere PEG-b-PCL Nanoparticles to Target Brain Capillary Endothelial Cells In Vitro. Journal of Nanomaterials, 2016. p. 7818501.

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Official URL: http://edoc.unibas.ch/43712/

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Abstract

Nanoparticles are increasingly used to implement drug targeting strategies. In the present study, solid-sphere nanoparticles (SNPs) made of poly(ethylene glycol)-b-poly(ε-caprolactone) (PEG-b-PCL) were covalently linked to a monoclonal antibody (83-14 mAb) targeted against the human insulin receptor that is highly expressed on human brain microvascular endothelial cells. Resulting targeted SNPs were characterized using transmission electron microscopy (TEM), cryo-TEM, dynamic light scattering, and fluorescence correlation spectroscopy. The critical aggregation concentration was determined using a fluorescence approach. Interaction with a well-characterized human in vitro model of the blood-brain barrier (hCMEC/D3) was analysed using an array of methods (flow cytometry, confocal laser scanning microscopy, and TEM). The toxicity on hCMEC/D3 cells and in addition on the human liver cell line HepG2 was assessed using the MTT assay. SNPs with a diameter of 80 nm and a homogeneous size distribution were obtained. Successful conjugation of 83-14 mAb using a heterobifunctional linker resulted in 5-6 molecules of fluorescently labeled 83-14 mAb per SNP. Functionalized SNPs were taken up by hCMEC/D3 cells efficiently without showing a significant toxic effect on cells of the blood-brain barrier and HepG2 cells. These results indicate that functionalized PEG-b-PCL SNPs are a promising candidate to deliver drugs to the CNS.
Faculties and Departments:05 Faculty of Science > Departement Pharmazeutische Wissenschaften > Pharmazie > Pharmazeutische Technologie (Huwyler)
UniBasel Contributors:Québatte, Gabriela and Grossen, Philip and Huwyler, Jörg and Baschong, Cristina and Witzigmann, Dominik
Item Type:Article, refereed
Article Subtype:Research Article
Publisher:Hindawi
ISSN:1687-4110
e-ISSN:1687-4129
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:03 Jan 2017 08:04
Deposited On:03 Jan 2017 08:04

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