A Numerical Model of Skin Electropermeabilization Based on In Vivo Experiments

Abstract

As an alternative to viral methods that are controversial because of their safety issues, chemical and physical methods have been developed to enhance gene expression in tissues. Reversible increase of the cell membrane permeability caused by the electric field--electroporation--is currently one of the most efficient and simple non-viral methods of gene transfer. We performed a series of in vivo experiments, delivering plasmids to rat skin using external plate electrodes. The experiments showed that skin layers below stratum corneum can be permeabilized in this way. In order to study the course of skin tissue permeabilization by means of electric pulses, a numerical model using the finite element method was made. The model is based on the tissue-electrode geometry and electric pulses used in our in vivo experiments. We took into account the layered structure of skin and changes of its bulk electrical properties during electroporation, as observed in the in vivo experiments. We were using tissue conductivity values found in literature and experimentally determined electric field threshold values needed for tissue permeabilization. The results obtained with the model are in good agreement with the in vivo results of gene transfection in rat skin. With the model presented we used the available data to explain the mechanism of the tissue electropermeabilization propagation beyond the initial conditions dictated by the tissue initial conductivities, thus contributing to a more in-depth understanding of this process. Such a model can be used to optimize and develop electrodes and pulse parameters.