Abstract

High-voltage pulsing has previously been shown to dramatically increase molecular transport across skin. The goal of this study was to examine the functional dependence of transdermal transport on pulse parameters and to make comparisons with iontophoresis. Transdermal transport of calcein, a model drug, was measured during low-voltage, constant electric fields (iontophoresis) and high-voltage pulsed electric fields (hypothesized to cause electroporation). In the first part of the study, the dependence of calcein flux caused by high-voltage pulses was determined as a function of pulse length, rate, polarity, waveform, and total pulsing time. In the second part, calcein transport numbers were calculated for both iontophoresis and high-voltage pulsing, and expressed as functions of pulse parameters. For both iontophoresis and high-voltage pulsing, transport numbers (or transport efficiency) ranged from 10^-5 to 10^-2 and were functions of voltage and current, but did not show dependence on pulse length, rate, energy, waveform, or total charge transferred. The resulting estimates of the area fraction of skin available to transport were larger during high-voltage pulsing ( 10^-3 for small ions and 10^-6 to 10^-3 for calcein) than during iontophoresis (10^-5 to 10^-4 for small ions and 10^-8 to 10^-4 for calcein).

Author Keywords: Electroporation; Iontophoresis; Transdermal drug delivery; Transport number; Transport pathway

Corresponding author: Massachusetts Institute of Technology, 77 Massachusetts Ave, , Cambridge, MA 02139, , USA. Tel. (617)-253-3123.

¹ Present address: School of Chemical Engineering, Georgia Institute of Technology, Atlanta, GA 30332-0100, USA. Tel. (404)-894-5135.