Skip to main content

Research Repository

Advanced Search

Drug delivery in a tumour cord model: a computational simulation

Hubbard, Matthew E.; Jove, M.; Loadman, P.M.; Phillips, R.M.; Twelves, C.J.; Smye, S.W.

Drug delivery in a tumour cord model: a computational simulation Thumbnail


Authors

MATTHEW HUBBARD MATTHEW.HUBBARD@NOTTINGHAM.AC.UK
Professor of Computational and Applied Mathematics

M. Jove

P.M. Loadman

R.M. Phillips

C.J. Twelves

S.W. Smye



Abstract

The tumour vasculature and microenvironment is complex and heterogeneous, contributing to reduced delivery of cancer drugs to the tumour. We have developed an in silico model of drug transport in a tumour cord to explore the effect of different drug regimes over a 72 h period and how changes in pharmacokinetic parameters affect tumour exposure to the cytotoxic drug doxorubicin. We used the model to describe the radial and axial distribution of drug in the tumour cord as a function of changes in transport rate across the cell membrane, blood vessel and intercellular permeability, flow rate, and the binding and unbinding ratio of drug within the cancer cells. We explored how changes in these parameters may affect cellular exposure to drug.

The model demonstrates the extent to which distance from the supplying vessel influences drug levels and the effect of dosing schedule in relation to saturation of drug binding sites. It also shows the likely impact on drug distribution of the aberrant vasculature seen within tumours. The model can be adapted for other drugs and extended to include other parameters. The analysis confirms that computational models can play a role in understanding novel cancer therapies to optimise drug administration and delivery.

Journal Article Type Article
Acceptance Date Apr 25, 2017
Publication Date May 24, 2017
Deposit Date Jun 16, 2017
Publicly Available Date Jun 16, 2017
Journal Royal Society Open Science
Electronic ISSN 2054-5703
Publisher The Royal Society
Peer Reviewed Peer Reviewed
Volume 4
DOI https://doi.org/10.1098/rsos.170014
Keywords Computational modelling, mathematical modelling, Drug delivery, Drug transport and binding, Pharmacokinetic resistance
Public URL https://nottingham-repository.worktribe.com/output/861669
Publisher URL http://rsos.royalsocietypublishing.org/content/4/5/170014

Files






You might also like



Downloadable Citations