Numerical study of therapeutic effectiveness of bolus injection and continuous infusion on drug delivery to vascularized solid tumor

Effective delivery of drugs to tumor cells is essential for the success of most anticancer therapies. In this study, two-dimensional modeling for spatiotemporal distribution of doxorubicin concentration under bolus injection and continuous infusion is presented. Mathematical simulations have been performed considering the main physical and biochemical processes in drug delivery to tumor cells. Anticancer effectiveness is evaluated through changes in tumor cell density based on predicted intracellular concentrations. Unlike most computational models of drug delivery to solid tumors, which assume a uniform distribution of blood vessels in the tumor, the vascular network as a fluid source term is produced using a sprouting angiogenesis method. The results demonstrate that the drugs accumulate more in areas with high vascular density, resulting in improved drug cytotoxicity. Compared to bolus injection, continuous injection leads to longer high level maintenance of intracellular drug concentrations in the tumor, which is more effective in improving the cytotoxic effect. Although bolus injection leads to a 90% higher extracellular concentration peak, there is the risk of severe side effects. According to the results, continuous injection by keeping doxorubicin at a relatively higher level for a longer period in the tumor leads to improved anticancer effectiveness about 26% relative to the effectiveness of bolus injection at the end of the treatment.