Influence of electric pulse characteristics on the cellular internalization of chemotherapeutic drugs and cell survival fraction in electroporated and vasoconstricted cancer tissues using boundary element techniques

Abstract

Electroporation has emerged as a suitable technique to induce the pore formation in the cell membrane of cancer tissues, facilitating the cellular internalization of chemotherapeutic drugs. An adequate selection of the electric pulse characteristics is crucial to guarantee the efficiency of this technique, minimizing the adverse effects. In the present work, the dual reciprocity boundary element method (DR-BEM) is applied for the simulation of drug transport in the extracellular and intracellular space of cancer tissues subjected to the application of controlled electric pulses, using a continuum tumour cord approach, and considering both the electro-permeabilization and vasoconstriction phenomena. The developed DR-BEM algorithm is validated with numerical and experimental results previously published, obtaining a satisfactory accuracy and convergence. Using the DR-BEM code, a study about the influence of the magnitude of electric field (E) and pulse spacing (d_pulses) on the time behavior and spatial distribution of the internalized drug, as well as on the cell survival fraction, is carried out. In general, the change of drug concentration, drug exposure and cell survival fraction with the parameters E and d_pulses is ruled by two important factors: the balance between the electro-permeabilization and vasoconstriction phenomena, and the relative importance of the sources of cell death (electric pulses and drug cytotoxicity); these two factors, in turn, significantly depend on the reversible and irreversible thresholds considered for the electric field.

Keywords: Boundary elements techniques; Cell survival rate; Cellular internalization; Chemotherapeutic drug transport; Electroporation; Vasoconstriction.