In-silico study about the influence of electroporation parameters on the chemotherapeutic drug transport in cancer tissues using the meshless method of approximate particular solutions

Abstract

Electroporation has become an important technique in cancer treatment to induce the drug internalization into cells by applying controlled electric pulses. In the present work, the simulation of transport of two chemotherapeutic drugs (doxorubicin and cisplatin) in electroporated cancerous tissues is carried out using the Global Method of Approximate Particular Solutions (Global MAPS), which is a meshless method having several computational advantages over finite element and finite volume methods commonly used in this kind of problems. Numerical parameters involved in Global MAPS simulations are calibrated by means of validation with results previously published in literature, points-number and time-step dependency analyses, and convergence analysis on a relaxation factor, obtaining satisfactory results. Voltage levels of 300 V, 350 V and 400 V, and pulse spacing of 10 s, 100 s and single pulse are considered as input electroporation parameters, whose influence on the following variables is analyzed: magnitude and distribution of electric field in the pulse stage; extracellular and intracellular concentrations of medicament in the pre-pulse and post-pulse diffusion stages, identifying different transport mechanism (internalization and extracellular diffusion) and the concentration equilibrium condition when reached; and efficiency and aggressiveness of the electroporation protocol. In general, numerical results point out that this influence highly depends on the drug type used during the electrochemotherapy treatment. • Transport simulation of drugs in electroporated cancer tissues using meshless technique. • Influence of voltage and pulse spacing on electric field, extracellular and intracellular concentrations. • Influence of voltage and pulse spacing on efficiency and aggressiveness of electroporation protocol. • Differences between cisplatin and doxorubicin behavior in pre-pulse and post-pulse diffusion stages. • Study of main transport mechanisms and concentration equilibrium condition for both drugs.