Skin electroporation for drug delivery involves the application of Pulsed Electric Fields (PEFs) on the skin to disrupt its barrier function in a temporary and non-invasive manner, increasing the uptake of drugs. It represents a potential alternative to delivery methods that are invasive (e.g. injections) or limited. We have developed a drug delivery system comprising nanocomposite hydrogels which act as a reservoir for the drug and an electrode for applying electric pulses on the skin. In this study, we employed a multi-scale approach to investigate the drug delivery system on a mouse skin model, through electrical measurements, numerical modeling and fluorescence microscopy. The Electrical properties indicated a highly non-linear skin conductivity behavior and were used to fine-tune the simulations and study skin recovery after electroporation. Simulation of electric field distribution in the skin showed amplitudes in the range of reversible tissue electroporation (400-1200 V/cm), for 300 V PEF. Fluorescence microscopy revealed increased uptake of fluorescent molecules compared to the non-pulsed control. We reported two reversible electroporation domains for our configuration:

(1) at 100 V PEF the first local transport regions appear in the extracellular lipids of the stratum corneum, demonstrated by a rapid increase in the skin's conductivity and an increased uptake of lucifer yellow, a small hydrophilic fluorophore and (2) at 300 V PEF, the first permeabilization of nucleated cells occurred, evidenced by the increased fluorescence of propidium iodide, a membraneimpermeable, DNA intercalating agent.