Skin electroporation: Rapid measurements of the transdermal voltage and flux of four fluorescent molecules show a transition to large fluxes near 50 V

Large molecular fluxes and tight control are highly desired for transdermal drug delivery, which motivated this study of molecular transport due to high voltage pulsing. We used a flow-through sampling system (time resolution of similar to 14 s) to measure the response of human skin in vitro to a series of exponential pulses (time constant of 1 ms; peak transdermal voltages [U-skin,U-0] of 0 V to similar to 300 V, one pulse every 5.6 s). Four negatively charged, hydrophilic fluorescent tracer molecules were employed: sulforhodamine, lucifer yellow, cascade blue, and calcein (molecular weights of 450 to 625 Da). Although differences in their molecular transport profiles were observed, all four molecules exhibited a transition from small to large fluxes at U-skin,U-0 approximate to 50 V. This behavior may reflect a transition from electroporation of the skin's appendages to electroporation of the multilamellar bilayer membranes within the stratum corneum.