Theoretical model of the influence of irreversibly electroporated cells on post pulse drug delivery to reversibly electroporated cells

Abstract

This study numerically investigates the drug uptake by a population that includes both reversibly and irreversibly electroporated cells. A theoretical continuum model is developed and simulations are conducted in conditions representing low porosity (cells in tissues) and high porosity (cells in suspension). This model considers only passive diffusion following the electroporation pulse and estimates the permeability increases of reversibly electroporated cells using empirically based predictions that relate the long-lived electropore density to the electric field magnitude. A parametric study investigates whether the permeability and resealing rate of irreversibly electroporated cells influence the delivery to the surviving reversibly electroporated cells. The results show that this influence is negligible when the cell number density is low (cells in dilute suspensions). For conditions of cells in tissue when both the fraction of the total cells that are irreversibly electroporated and the permeability of the irreversibly electroporated cells are high enough, the irreversibly electroporated cells rapidly take up the drug and deplete the extracellular space of the available drug. This lowered extracellular concentration can result in less drug delivery to reversibly electroporated cells.

Keywords: cell; drug delivery; electroporation; mathematical; numerical; population; tissue.