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Chemical Engineering Science, Vol.208, 2019
Numerical investigation of drug transport from blood vessels to tumour tissue using a Tumour-Vasculature-on-a-Chip
Delivery of adequate amount of anticancer drugs to tumour sites is critical to achieve effective therapeutic treatment, but it remains challenging to observe drug transport and investigate the spatial distribution of the drug in tumour microenvironment experimentally. In this study, we investigated the drug transport from a blood vessel to a tumour tissue, and explored the effect of tumour size, tumour numbers and positioning on drug concentration distribution using a numerical method in combination with a microfluidic Tumour-Vasculature-on-a-Chip (TVOC) model. The TVOC model is composed of a blood vessel channel, and a tumour channel sandwiched with a porous membrane. A species transport model based on computational fluid dynamics was adopted to investigate drug transport. The numerical simulation was firstly validated using experimental data, and then used to analyse the spatial-temporal structure of the flow, and to investigate the effect of tumour size and positioning on drug transport and drug concentration heterogeneity. We found the drug concentration surrounding the tumour was highly heterogeneous, with the most downstream point the most difficult for drugs to transport and the nearest point to the blood vessel the easiest. Moreover, tumour size and positioning contributed significantly to this drug concentration heterogeneity on tumour surface, which was dramatically augmented in large and downstream-positioned tumours. These studies established the relationship between solid tumour size/positioning and drug concentration heterogeneity in the tumour microenvironment, which could help to understand heterogeneous drug distribution in tumour microenvironment. (C) 2019 Elsevier Ltd. All rights reserved.
Keywords:Drug transport;Numerical investigation;Tumour-Vasculature-on-a-Chip;Species transport model