Feasibility of an electrode-reservoir device for transderrnal drug delivery by noninvasive skin electroporation

Electrical creation of aqueous pathways across the skin's outer layer [stratum corneum (SC)] provides an approach to transdermal delivery of medium-size water-soluble compounds. However, nerve stimulation should be avoided. Here, we show that a microstructured electrode array can significantly confine the electric field to the nerve-free SC. The prototype electrode-reservoir device (ERD) contains field-confining electrodes and a fluorescent drug surrogate [sulphorhodamine (SR)]. In vivo human experiments at the forearm with approximately rectangular voltage pulses up to 500 V and 1-ms duration cause electroporation as measured by skin resistance change but only rarely caused sensation. Human skin in vitro experiments with such pulses up to 300 V transported SR across the SC. Our results are supported by a model's prediction of the field in the ERD and nearby tissue.