Abstract
Background The 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. Methods The 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. Results Sensitivity 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. Conclusions This 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.
Highlights
The 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
Simulation of interstitial fluid flow for baseline values (Table 1) predicts that interstitial fluid pressure (IFP) has its greatest value in the tumor center
Results show that interstitial fluid velocity (IFV), IFP, and drug concentration in interstitial fluid (DCIF) are sensitive to tissue hydraulic conductivity changes
Summary
The 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. Chemotherapy is one of the ways widely used for cancer treatment. Based on the findings from clinical applications, most cancer treatments with drugs fail to eliminate solid tumors completely [3]. The computational method can investigate why systemic administration cannot distribute drug uniformly in tumors.
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