Mass transfer model for drug delivery in tissue cells with reversible electroporation

Reversible electroporation is the temporary permeabilization of the cell membrane through the formation of nano-scale pores that are transient defects in the membrane. These pores are caused by short electrical pulses, typically on the order of a few to several hundred microseconds that are delivered by electroporation electrodes inserted around the treated tissue. Reversible electroporation has become an important technique in molecular medicine. It is used to introduce macromolecules such as genes or anticancer drugs, to which the cell membrane is normally not permeable, into the cytosol. For optimal application of molecular medicine, it is important to be able to predict precisely the mass transfer in tissue during reversible electroporation. In this study, we introduce a first attempt at developing a macroscopic mathematical model for analyzing the mass transfer into cells during reversible electroporation of tissue. The model combines a macroscopic model of the electrical fields around electroporation electrodes with a new cells-scale model of electroporation-driven mass transfer and with a macroscopic mass transfer model in tissue. The model is illustrated for a situation typical to that in electrochemotherapy in which cancer is treated with reversible electroporation and a non cell membrane permeant drug such as bleomycin.