No / 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.
| Identifer | oai:union.ndltd.org:BRADFORD/oai:bradscholars.brad.ac.uk:10454/10002 |
| Date | 12 March 2014 |
| Creators | Groh, C.M., Hubbard, M.E., Jones, P.F., Loadman, Paul, Periasamy, Nagarajan, Sleeman, B.D., Smye, S.W., Twelves, Christopher J., Phillips, Roger M. |
| Source Sets | Bradford Scholars |
| Language | English |
| Detected Language | English |
| Type | Article, No full-text in the repository |
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