ELECTROPORATION OF HUMAN SKIN - SIMULTANEOUS MEASUREMENT OF CHANGES IN THE TRANSPORT OF 2 FLUORESCENT MOLECULES AND IN THE PASSIVE ELECTRICAL-PROPERTIES

The stratum corneum (SC) of mammalian skin is a formidable barrier to the transport of both small ions and charged molecules, but large, ver y rapid increases in transport can be created by ''high-voltage'' puls es. Here a series of exponential pulses (tau(pulse) = 1.1 ms) was used in vitro with human skin preparations. A flow-through apparatus provi ded simultaneous, continuous measurements for the transport of two flu orescent molecules (calcein, 623 Da, charge of z(cal) = -4; sulforhoda mine, 607 Da, charge of z(sr) = -1) and the skin's passive electrical properties, with emphasis on the transdermal conductive behavior, whic h includes both the d.c. conductance, G(skin), and the non-linear dyna mic conductance, G(dy). ''High-voltage'' pulsing was found to cause la rge and very rapid changes in the molecular flux of both molecules, an d also in G(skin) and G(dy). In the case of molecular transport, the r elative contribution of local diffusion and local electric field-drive n transport depends significantly on the molecular charge, z(s). The f ield-driven transport during a pulse allowed estimates of the maximum fractional aqueous area, F-w,F-s, of the skin that was transiently ava ilable during a pulse for small ions (F-w,F-ions = 6 +/- 3 X 10(-4)), calcein (F-w,(cal) = 5 +/- 3 X 10(-5)), and sulforhodamine (F-w,F-sr = 7 +/- 4 X 10(-5)). Comparison of the post-pulse recovery of G(skin) a nd the decrease of the molecular transport showed that the recovery of the skin barrier and molecular flux decay are not identical. These re sults are interpreted as being due to electrical creation of new aqueo us pathways (''pores'') across the lipid regions of the skin's stratum corneum, and support the hypothesis that electroporation is responsib le for the rapid and large changes observed.