Effect of tumor shape, size, and tissue transport properties on drug delivery to solid tumors

Abstract

BackgroundThe computational methods provide condition for investigation related to the process of drug delivery, such as convection and diffusion of drug in extracellular matrices, drug extravasation from microvessels or to lymphatic vessels. The information of this process clarifies the mechanisms of drug delivery from the injection site to absorption by a solid tumor. In this study, an advanced numerical method is used to solve fluid flow and solute transport equations simultaneously to investigate the effect of tumor shape and size on drug delivery to solid tumor.MethodsThe advanced mathematical model used in our previous work is further developed by adding solute transport equation to the governing equations. After applying appropriate boundary and initial conditions on tumor and surrounding tissue geometry, the element-based finite volume method is used for solving governing equations of drug delivery in solid tumor. Also, the effects of size and shape of tumor and some of tissue transport parameters such as effective pressure and hydraulic conductivity on interstitial fluid flow and drug delivery are investigated.ResultsSensitivity analysis shows that drug delivery in prolate shape is significantly better than other tumor shapes. Considering size effect, increasing tumor size decreases drug concentration in interstitial fluid. This study shows that dependency of drug concentration in interstitial fluid to osmotic and intravascular pressure is negligible.ConclusionsThis study shows that among diffusion and convection mechanisms of drug transport, diffusion is dominant in most different tumor shapes and sizes. In tumors in which the convection has considerable effect, the drug concentration is larger than that of other tumors at the same time post injection.

Multistep, effective drug distribution within solid tumors

“…Step functions (with rounded edges) are widely used in simulations of systemic delivery [20, 32]. In step functions the IFP profiles essentially are a plateau of constant value from the tumor center to the tumor edge (where a tumor tissue meets a vessel wall) and sharply drop along the vessel wall.…”

“…In step functions the IFP profiles essentially are a plateau of constant value from the tumor center to the tumor edge (where a tumor tissue meets a vessel wall) and sharply drop along the vessel wall. Indeed, in such simulations the drug transport, which is oriented inward upstream against the IFP gradient, was found to be dominated by diffusion and not convection [32]. …”

MRI contrast agent concentration and tumor interstitial fluid pressure

“…, which is the ratio of convection to diffusion across the capillary wall (Baxter and Jain, 1989;Curry, 1984;Sefidgar et al, 2014). P is the permeability coefficient of the blood vessels,  the osmotic reflection coefficient of the contrast agent, and C p the concentration of contrast agent within the plasma.…”

Numerical simulation of the tumor interstitial fluid transport: Consideration of drug delivery mechanism

“…Zhao et al (2007) and Pishko et al (2011) simulated drug delivery through specific tumorous tissue, which had been obtained from MRI technique and examined effects of heterogeneous vasculature and porosity. Recently, Chen (2011,2012) and Sefidgar et al (2014) have studied effects of various tumor configurations and transport properties on drug distribution by incorporating fluid and concentration equations.…”