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Lookup NU author(s): David Bourne, Professor Moein MoghimiORCiD
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© 2019, © 2019 Informa UK Limited, trading as Taylor & Francis Group. Targeting of nanoparticles to tumours can potentially improve the specificity of imaging and treatments. We have developed a multicompartmental pharmacokinetic model in order to analyse some of the factors that control efficiency of targeting to intravascular (endothelium) and extravascular (tumour cells and stroma) compartments. We make the assumption that transport across tumour endothelium is an important step for subsequent nanoparticle accumulation in the tumour (area-under-the-curve, AUC) regardless of entry route (interendothelial and transendothelial routes) and study this through a multicompartmental simulation. Our model reveals that increasing endothelial targeting efficiency has a much stronger effect on the AUC than increasing extravascular targeting efficiency. Furthermore, our analysis reveals that both extravasation and intratumoral diffusion rates need to be increased in order to significantly increase the AUC of extravascular-targeted nanoparticles. Increasing the nanoparticle circulation half-life increases the AUC independently of extravasation and intratumoral diffusion. Targeting the extravascular compartment leads to a buildup in the first layer surrounding blood vessels at the expense of deeper layers (binding site barrier). This model explains some of the limitations of tumour targeting and provides important guidelines for the design of targeted nanomedicines.
Author(s): Benchimol MJ, Bourne D, Moghimi SM, Simberg D
Publication type: Article
Publication status: Published
Journal: Journal of Drug Targeting
Year: 2019
Volume: 27
Issue: 5-6
Pages: 690-698
Online publication date: 07/01/2019
Acceptance date: 23/11/2018
ISSN (print): 1061-186X
ISSN (electronic): 1029-2330
Publisher: Taylor and Francis
URL: https://doi.org/10.1080/1061186X.2019.1566339
DOI: 10.1080/1061186X.2019.1566339
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