Simulation of the role of the anti-angiogenic therapy in fluid flow behavior and macromolecule transport into a heterogeneous solid tumor

The present study develops a numerical approach based on the mathematical models governing the behavior of fluid flow and drug transport in tumors to investigate the delivery of a macromolecule (IgG) under the effect of the vascular normalization into a non-uniform tumor, including different parts of a real solid tumor. In this study, different sizes of tumor in the range of 0.23≤R_eq≤2.79cm is considered. The area under the curves of the drug average distribution and its deviation in the tumor site over time is studied as the amount of drug delivered and uniformity of delivered drug to assess the quality of drug delivery. Results show that before and after normalization, the behavior of interstitial fluid flow and the distribution of therapeutic agent concentration depends on the tumor size. Normalization in all sizes reduces the interstitial fluid pressure, which this pressure drop increases as the tumor size reduces. Normalization improves the antibody concentration distribution at different times depending on the tumor size. However, from the point of view of the average spatiotemporal criterion, vascular normalization improves IgG delivery into the tumor site in 0.46≤R_eq≤0.93cm by increasing the distribution uniformity. This research, by discussing the mechanisms affecting the normalization efficiency, can provide insights for in vivo and in vitro studies that address the combination of anti-angiogenic therapy and chemotherapy.