Penetration and distribution efficacy of chemotherapeutic drugs in biological tissues: A computational investigation

Abstract

Many chemotherapeutic drugs, developed so far, show significant anticancer activities during the clinical trials; however, their treatment efficacy is limited in practice. The limited efficacy is attributed to the inadequate knowledge of interplay between a drug and the physicochemical properties of tissues. This study employs the finite volume heterogeneous multiscale method to study the penetration and distribution efficacy of chemotherapeutic agents such as, fluorouracil, carmustine, cisplatin, methotrexate, doxorubicin, and paclitaxel. The physical properties of these drugs are incorporated in the model to provide physiological scenario. The effects of fluid flow, drug elimination, and microscopic cellular structures are analysed on penetration and distribution of these chemotherapeutic drugs. It is observed that carmustine penetrates deeper into the tissue, followed by paclitaxel, methotrexate, fluorouracil, doxorubicin, whereas cisplatin penetrates least. In order to explain advection–diffusion–reaction processes, a novel dimensionless number KT=Ka/Th2 is introduced, where Ka and Th are Karlovitz and Thiele modulus numbers, respectively. This number may be defined as the ratio of time-scale of reaction rate with the cumulative time-scale of advection and diffusion processes. As the model involves several parameters, the global sensitivity analysis is also performed to determine the sensitivity of uncertainties in the input parameters to the model output.