Drug delivery in a tumour cord model: a computational simulation

The tumour vasculature and microenvironment is complex and heterogeneous, contributing to reduced delivery of cancer drugs to the tumour. We have developed an in silico model of drug transport in a tumour cord to explore the effect of different drug regimes over a 72 h period and how changes in pharmacokinetic parameters affect tumour exposure to the cytotoxic drug doxorubicin. We used the model to describe the radial and axial distribution of drug in the tumour cord as a function of changes in the transport rate across the cell membrane, blood vessel and intercellular permeability, flow rate, and the binding and unbinding ratio of drug within the cancer cells. We explored how changes in these parameters may affect cellular exposure to drug. The model demonstrates the extent to which distance from the supplying vessel influences drug levels and the effect of dosing schedule in relation to saturation of drug-binding sites. It also shows the likely impact on drug distribution of the aberr...肿瘤血管系统与肿瘤微环境结构复杂且异质性强，可降低抗癌药物向肿瘤部位的递送效率。本研究构建了肿瘤索内药物转运的计算机模拟（in silico）模型，用于探究72小时周期内不同给药方案的效果，以及药代动力学参数变化如何影响肿瘤对细胞毒性药物阿霉素（doxorubicin）的暴露量。我们借助该模型描述了肿瘤索内药物的径向与轴向分布随跨细胞膜、血管及细胞间通透性的转运速率、血流速率，以及癌细胞内药物结合与解离比率变化的规律，并探究了上述参数的变化对细胞药物暴露量的影响。该模型阐明了肿瘤与供血血管的距离对药物浓度的影响程度，以及给药方案与药物结合位点饱和状态的关联效应。此外，该模型还揭示了异常因素对药物分布的潜在影响。