A Computational Study of Doxorubicin Transport in a Tumor Microenvironment: Influence of Interstitial Fluid Pressure

Abstract

Interstitial fluid pressure (IFP) increases in solid tumors, which drives the convective flow away from the tumor center, preventing penetration of chemotherapy. A convection-diffusion-reaction model coupled with the Darcy-Starling equation was used to model the motion of Doxorubicin in a 1 cm radius tumor. The IFP was analytically obtained based on the modified spherical Bessel equation, and checked numerically, with a maximum residual error of less than 10^-8 Pa. Results show an outward flow velocity up to 43.75 nm s^-1 within a peripheral shell of 0.31 mm accompanied by tumor core IFP of 5 mmHg. At t = 3 h, drug concentrations were 19% of plasma peak with a steady rim-to-core gradient. A parametric study varying vascular pressure (600-3000 Pa) verified that bulk drug supply is regulated by transvascular supply while IFP regulates the peripheral concentration gradient. The results support the vascular normalization strategy to improve intratumoral drug delivery.