Abstract
Drug transport and its uptake by tumour cells are strongly dependent on tumour properties, which vary in different types of solid tumours. By simulating the key physical and biochemical processes, a numerical study has been carried out to investigate the transport of anti-cancer drugs in 3-D tumour models of different sizes. The therapeutic efficacy for each tumour is evaluated by using a pharmacodynamics model based on the predicted intracellular drug concentration. Simulation results demonstrate that interstitial fluid pressure and interstitial fluid loss vary non-linearly with tumour size. Transvascular drug exchange, driven by the concentration gradient of unbound drug between blood and interstitial fluid, is more efficient in small tumours, owing to the low spatial-mean interstitial fluid pressure and dense microvasculature. However, this has a detrimental effect on therapeutic efficacy over longer periods as a result of enhanced reverse diffusion of drug to the blood circulation after the cessation of drug infusion, causing more rapid loss of drug in small tumours.
| Original language | English |
|---|---|
| Article number | e0172276 |
| Number of pages | 16 |
| Journal | PloS ONE |
| Volume | 12 |
| Issue number | 2 |
| DOIs | |
| Publication status | Published - 17 Feb 2017 |
Bibliographical note
This work was partially funded by the UK Engineering and Physics Sciences ResearchCouncil (EP/I001700/1) to XYX. The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
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