In-silico research on the effects of variable voltage pulse protocols on the cell survival and permeabilization fractions in electroporated cancerous tissues

Abstract

Reversible electroporation is used to increase the cell membrane permeability by the application of short duration, high voltage electric pulses with electrodes strategically positioned to induce localized drug concentration in the tumor tissue. However, inadequate selection of pulses’ characteristics can lead to relevant loss of cell viability or lack of cell permeabilization, affecting aversively the results of the therapy. Accordingly, the balance between cell membrane electro-permeabilization and cell death is crucial, and the recursive modification of electroporation parameters can favor this balance to increase the drug uptake into viable cells. Particularly, the controlled diminution of the voltage level as the number of pulses increases can reduce the cell damage without compromising the membrane electro-permeabilization. In this work, a previously developed in-silico tool, based on the Global Method of Approximate Particular Solutions (GMAPS), is calibrated, validated, and used to study the differences between constant voltage and variable voltage pulse protocols (CVP and VVP) in terms of the magnitude and distribution of cell survival and permeabilization fractions along the tissue domain, and the internalization efficiency of the therapy. In VVP protocols, the reduction of the applied voltage with the number of pulses is numerically estimated to reach a target volume-averaged survival fraction in the most sensitive zone of the tissue. Numerical results indicate that differences between the pulse protocol types (CVP and VVP) depend on the initial voltage level ∅0 and number of pulses K, with the VVP protocol bringing about superior results for the larger values of ∅0 and K considered here.