The Open UniversitySkip to content
 

Toxicity and internalization of polymeric nanoparticles in brain endothelial cells

Silva de Abreu, Marcelle; Calpena, Ana C.; Espina, Marta; Garcia, Maria Luisa; Romero, Ignacio A. and Male, David (2017). Toxicity and internalization of polymeric nanoparticles in brain endothelial cells. In: Fluids and Barriers of the CNS, BioMed Central, 14(Supp2) p. 19.

Google Scholar: Look up in Google Scholar

Abstract

The blood brain barrier (BBB) is a barrier that protects the brain against various harmful substances. However, it is an important limitation for the development of new drugs. For this reason, there is a constant search in find new alternatives to deliver drugs to the brain. In this way, polymeric nanoparticles (NPs) from (D,L-lactide-co-glycolide) poly(ethylene glycol) (PLGA-PEG) could be an important strategy to facilitate the transport of therapeutic molecules across the BBB; they are a drug delivery systems that is biodegradable, biocompatible and approved by Food and Drug Administration (FDA). The main objective of this work was the encapsulation of an anti-diabetic drug in polymeric NPs of PLGA-PEG to analyze its toxicity and internalization using a human brain microvascular endothelial cell line (hCMEC/D3). The NPs were prepared by the solvent displacement technique. An initial study used a factorial design to modify the independent variables determining NP synthesis. Subsequently, physicochemical, biopharmaceutical and stability characterization studies were done. To evaluate the toxicity and uptake, NPs, at concentrations up to 10 µg/mL, were applied to the hCMEC/D3 cell line. Uptake was measured by flow cytometry (FACSCalibur) with rhodamine-labelled NPs. The experiment was standardized to 10,000 events on the gate and at voltage of 410 mV with respect to the control sample (untreated cells). The results demonstrated that the NPs (mean size around 160 nm and negative charge of −14.4 mV), were internalized by the cells, and showed the character of a monodisperse systems. The release profile showed a slow release with a Fick’s passive diffusion. In the toxicity assay, cells were 80% viable up to a concentration of 5 µg/mL. Fluorescence and electron microscopy indicated that NPs were primarily present in the cells’ cytosol. Taken together, the results demonstrate that these nanoparticles could be effective in delivering therapeutics to the central nervous system.

Item Type: Conference or Workshop Item
Copyright Holders: 2017 The Authors
ISSN: 2045-8118
Project Funding Details:
Funded Project NameProject IDFunding Body
Nanocarrier transport across the blood brain barrierNot SetSantander
Keywords: nanoparticles; blood brain barrier
Academic Unit/School: Faculty of Science, Technology, Engineering and Mathematics (STEM) > Life, Health and Chemical Sciences
Faculty of Science, Technology, Engineering and Mathematics (STEM)
Research Group: Innovation, Knowledge & Development research centre (IKD)
Related URLs:
Item ID: 52216
Depositing User: David Male
Date Deposited: 06 Nov 2017 09:26
Last Modified: 07 Dec 2018 10:58
URI: http://oro.open.ac.uk/id/eprint/52216
Share this page:

Actions (login may be required)

Policies | Disclaimer

© The Open University   contact the OU