A numerical model of skin electroporation as a method to enhance gene transfection in skin

Abstract

Electroporation is an effective alternative to viral methods to significantly improve DNA transfection after intradermal and topical delivery. We performed a series of in vivo experiments on 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 was built, with COMSOL Multiphysics, using the finite element method. The model is based on the tissue-electrode geometry and electric pulses from our in vivo experiments. We took into account the layered structure of skin and changes of its bulk electric 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 were then compared to the in vivo results of gene transfection in rat skin and a good agreement was obtained. With the model presented we used the available data to try to explain the mechanism of the tissue electropermeabilization propagation beyond the initial conditions dictated by the tissue initial specific conductivities.