The Influence of Irreversibly Electroporated Cells on Post Pulse Drug Delivery to Reversibly Electroporated Cells

Abstract

Electroporation can result in cell death in some proportion of a population of cells and, because the nature of the membrane disruption can vary significantly in irreversibly electroporated cells, there is uncertainty in the magnitude of and the transient behaviour of the associated permeability increases. This study numerically investigates the drug uptake by a population of cells that includes both reversibly and irreversibly electroporated cells. A theoretical continuum model is developed and simulations are conducted in conditions of low porosity (cells in tissues) and of high porosity (cells in suspension). This model estimates the permeability increases of electroporated cells using empirically based predictions of the dependence of long-lived electropore density on the local electric field magnitude. A parametric investigation investigates how the transmembrane transport characteristics of irreversibly electroporated cells (permeability and resealing rate) affect the drug uptake of the surviving cells. The results show that the magnitude and duration of the permeability increases of irreversibly electroporated cells is much more influential in low porosity tissues than in high porosity dilute suspensions. In applications of electroporation of cells in tissues, the uncertainty of irreversibly electroporated cells should be considered in regions of tissue experiencing field strengths for which the fraction of the total cells that are irreversibly electroporated exceeds about 0.1.