Non-linearity of molecular transport through human skin due to electric stimulus

The multilamellar bilayer system of the skin's stratum corneum (SC) provides the main barrier to transdermal transport of ions and charged molecules. Electrically driven transport of charged species at low trans-SC voltages (U(SC)<5 V) occurs predominantly via pre-existing aqueous pathways. In contrast, high voltage, (HV; U(SC)>50 V) has been hypothesized to involve electroporation within the SC's multilamellar bilayer membranes, creating new aqueous pathways that contribute to a rapid, large increase in transport. Thus, it might be expected that HV-pulses would always increase subsequent iontophoresis. Here we show, however, that for some charged molecules the opposite occurs, because the low skin resistance due to new aqueous pathways leads to an actual decrease in U(SC) for the same applied current, and the transport of some, highly charged molecules has a highly nonlinear dependence on U(SC).