Transport of a charged molecule across the human epidermis due to electroporation

Transport of a charged molecule (calcein; z = 4 ; 623 g/mol) across the epidermis can be caused and controlled by an electric pulse protocol. Our interpretation is that the stratum corneum (SC) is altered by the field, such that a series of regularly spaced exponential electric field pulses (time constant Zpu~se= 1.1 ms) resulting in Usk~n= 80--230 V causes a tremendous enhancement in molecular transport. Upon beginning a pulse protocol, the flux increases from negligible values, and exponentially approaches a quasi-steady state flux with a lag time constant, ~'~ag, that depends on the pulse spacing, but not the transdermal voltage magnitude. Above a threshold of Usk~, = 80 V across the skin for the pulse conditions used here, molecular transport increases almost linearly with Usk~n, and then levels off at higher voltages ( U~k~, > 250 V) or shorter spacing ( < 10 s). When pulsing is stopped, the flux decreases by an order of magnitude within 1 min. Once the quasi-steady state is reached, it is stable for at least 6 h. For a particular specimen, the maximum flux depends on the peak voltage across the skin, the pulse time constant and the pulse spacing. Measurements of the passive electrical properties were carried out simultaneously in order to independently characterize the skin in terms of its altered ability to transport small ions.