In vivo pharmacokinetics of T2 contrast agents based on iron oxide nanoparticles: optimization of blood circulation times

Leal, M. P., Muñoz-Hernández, C., Berry, C. and García-Martín, M. L. (2015) In vivo pharmacokinetics of T2 contrast agents based on iron oxide nanoparticles: optimization of blood circulation times. RSC Advances, 5(94), pp. 76883-76891. (doi: 10.1039/C5RA15680G)

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Abstract

Magnetic nanoparticles have been extensively investigated for in vivo nanomedical applications in the last decade. PEG coating improves the solubility and stability of the nanoparticles, and provides stealth properties by preventing opsonization and subsequent removal by the reticuloendothelial system. All these effects conferred by the PEG coating are dependent on its molecular weight. Therefore, the selection of the right MW of PEG is a crucial point in the design of new nanomaterials for in vivo applications. The aim of this work lies in the in vivo optimization of the circulation times of small iron oxide nanoparticles by coating them with PEG of different MWs. PEGylated small superparamagnetic iron oxide nanoparticles (PEG-SPIONs), using PEG MWs ranging from 600 to 8000, were synthesized following a ligand exchange methodology, resulting in highly stable and water-soluble nanoparticles. Semi-quantitative and quantitative MRI studies allowed us to track the pharmacokinetics and biodistribution of intravenously injected PEG-SPIONs (HD < 50 nm) in vivo up to one week. Results show that high MW PEGs (6000–8000) lead to nanoparticle aggregation and low MW PEGs (≤1500) are not able to stabilize the 6 nm iron oxide nanoparticles in physiological medium or confer stealth properties, thus leading to rapid recognition by the RES. In contrast, PEG3000-SPIONs show excellent in vivo behavior, they do not aggregate and they exhibit better stealth properties, giving rise to slower liver uptake and longer circulation times. In conclusion, 3000 Da turned out to be the optimal MW for the PEGylation of small nanoparticles (∼6 nm) designed for biomedical applications in which long circulation times together with moderate liver uptake are desirable.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Berry, Dr Catherine
Authors: Leal, M. P., Muñoz-Hernández, C., Berry, C., and García-Martín, M. L.
College/School:College of Medical Veterinary and Life Sciences > Institute of Molecular Cell and Systems Biology
Journal Name:RSC Advances
Publisher:Royal Society of Chemistry
ISSN:2046-2069
ISSN (Online):2046-2069
Published Online:01 September 2015
Copyright Holders:Copyright © 2015 The Royal Society of Chemistry
First Published:First published in RSC Advances 5(94): 76883-76891
Publisher Policy:Reproduced under a Creative Commons License

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