Mathematical and computational models of drug transport in tumours
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...
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| Format: | Article |
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Royal Society
2014
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| Online Access: | https://eprints.nottingham.ac.uk/40819/ |
| _version_ | 1848796140137349120 |
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| author | Groh, C.M. Hubbard, Matthew E. Jones, P.F. Loadman, P.M. Periasamy, N. Sleeman, B.D. Smye, S.W. Twelves, C.J. Phillips, R.M. |
| author_facet | Groh, C.M. Hubbard, Matthew E. Jones, P.F. Loadman, P.M. Periasamy, N. Sleeman, B.D. Smye, S.W. Twelves, C.J. Phillips, R.M. |
| author_sort | Groh, C.M. |
| building | Nottingham Research Data Repository |
| collection | Online Access |
| description | 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. |
| first_indexed | 2025-11-14T19:43:15Z |
| format | Article |
| id | nottingham-40819 |
| institution | University of Nottingham Malaysia Campus |
| institution_category | Local University |
| last_indexed | 2025-11-14T19:43:15Z |
| publishDate | 2014 |
| publisher | Royal Society |
| recordtype | eprints |
| repository_type | Digital Repository |
| spelling | nottingham-408192020-05-04T16:44:52Z https://eprints.nottingham.ac.uk/40819/ Mathematical and computational models of drug transport in tumours Groh, C.M. Hubbard, Matthew E. Jones, P.F. Loadman, P.M. Periasamy, N. Sleeman, B.D. Smye, S.W. Twelves, C.J. Phillips, R.M. 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. Royal Society 2014-03-12 Article PeerReviewed Groh, C.M., Hubbard, Matthew E., Jones, P.F., Loadman, P.M., Periasamy, N., Sleeman, B.D., Smye, S.W., Twelves, C.J. and Phillips, R.M. (2014) Mathematical and computational models of drug transport in tumours. Interface, 11 (94). 20131173/1-20131173/14. ISSN 1742-5662 Computational modelling; Mathematical modelling; Drug delivery; Drug transport; Drug binding; Pharmacokinetic profiles http://rsif.royalsocietypublishing.org/content/11/94/20131173 doi:10.1098/rsif.2013.1173 doi:10.1098/rsif.2013.1173 |
| spellingShingle | Computational modelling; Mathematical modelling; Drug delivery; Drug transport; Drug binding; Pharmacokinetic profiles Groh, C.M. Hubbard, Matthew E. Jones, P.F. Loadman, P.M. Periasamy, N. Sleeman, B.D. Smye, S.W. Twelves, C.J. Phillips, R.M. Mathematical and computational models of drug transport in tumours |
| title | Mathematical and computational models of drug transport in tumours |
| title_full | Mathematical and computational models of drug transport in tumours |
| title_fullStr | Mathematical and computational models of drug transport in tumours |
| title_full_unstemmed | Mathematical and computational models of drug transport in tumours |
| title_short | Mathematical and computational models of drug transport in tumours |
| title_sort | mathematical and computational models of drug transport in tumours |
| topic | Computational modelling; Mathematical modelling; Drug delivery; Drug transport; Drug binding; Pharmacokinetic profiles |
| url | https://eprints.nottingham.ac.uk/40819/ https://eprints.nottingham.ac.uk/40819/ https://eprints.nottingham.ac.uk/40819/ |