TRANSPORT OF A CHARGED MOLECULE ACROSS THE HUMAN EPIDERMIS DUE TO ELECTROPORATION

Transport of a charged molecule (calcein; z = -4; 623 g/mol) across th e epidermis can be caused and controlled by an electric pulse protocol . Our interpretation is that the stratum corneum (SC) is altered by th e field, such that a series of regularly spaced exponential electric f ield pulses (time constant tau(pulse) = 1.1 ms) resulting in U-skin ap proximate to 80-230 V causes a tremendous enhancement in molecular tra nsport, Upon beginning a pulse protocol, the flux increases from negli gible values, and exponentially approaches a quasi-steady state flux w ith a lag time constant, tau(lag) that depends on the pulse spacing, b ut not the transdermal voltage magnitude. Above a threshold of U-skin approximate to 80 V across the skin for the pulse conditions used here , molecular transport increases almost linearly with U-skin, and then levels off at higher voltages (U-skin > 250 V) or shorter spacing (< 1 0 s). When pulsing is stopped, the flux decreases by an order of magni tude within 1 min. Once the quasi-steady state is reached, it is stabl e for at least 6 h. For a particular specimen, the maximum flux depend s 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.