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    Mathematical and computational models of drug transport in tumours

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    Publication date
    2014-05-06
    Author
    Groh, C.M.
    Hubbard, M.E.
    Jones, P.F.
    Loadman, Paul M.
    Periasamy, Nagarajan
    Sleeman, B.D.
    Smye, S.W.
    Twelves, Christopher J.
    Phillips, Roger M.
    Keyword
    Computational modelling; Mathematical Modelling; Drug delivery; Drug transport; Drug binding; Pharmacokinetic profiles
    Peer-Reviewed
    Yes
    
    Metadata
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    Abstract
    The ability to predict how far a drug will penetrate into the tumour microenvironment within its pharmacokinetic (PK) lifespan would provide valuable information about therapeutic response. As the PK profile is directly related to the route and schedule of drug administration, an in silico tool that can predict the drug administration schedule that results in optimal drug delivery to tumours would streamline clinical trial design. This paper investigates the application of mathematical and computational modelling techniques to help improve our understanding of the fundamental mechanisms underlying drug delivery, and compares the performance of a simple model with more complex approaches. Three models of drug transport are developed, all based on the same drug binding model and parametrized by bespoke in vitro experiments. Their predictions, compared for a ‘tumour cord’ geometry, are qualitatively and quantitatively similar. We assess the effect of varying the PK profile of the supplied drug, and the binding affinity of the drug to tumour cells, on the concentration of drug reaching cells and the accumulated exposure of cells to drug at arbitrary distances from a supplying blood vessel. This is a contribution towards developing a useful drug transport modelling tool for informing strategies for the treatment of tumour cells which are ‘pharmacokinetically resistant’ to chemotherapeutic strategies.
    URI
    http://hdl.handle.net/10454/10002
    Version
    No full-text in the repository
    Citation
    Groh CM, Hubbard ME, Jones PF et al (2014) Mathematical and computational models of drug transport in tumours. Journal of the Royal Society Interface. 11(94)
    Link to publisher’s version
    http://dx.doi.org/10.1098/rsif.2013.1173
    Type
    Article
    Collections
    Life Sciences Publications

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