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 approximately 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 [Uskin,0] of 0 V to approximately 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 Uskin,0 approximately 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.
Chen
T
T
Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA. tanichen@mit.edu
Segall
E M
EM
Langer
R
R
Weaver
J C
JC
D018274:Electroporation; D005452:Fluoresceins / Q000378:metabolism; D005456:Fluorescent Dyes / Q000378:metabolism*; D006801:Humans; D007546:Isoquinolines / Q000378:metabolism; D009942:Organometallic Compounds / Q000378:metabolism; D009943:Organophosphorus Compounds / Q000378:metabolism; D012867:Skin / Q000378:metabolism; D012869:Skin Absorption; D012879:Skin Physiological Phenomena
D005452:Fluoresceins; D005456:Fluorescent Dyes; D007546:Isoquinolines; D009942:Organometallic Compounds; D009943:Organophosphorus Compounds; C066850:Cascade Blue; C017475:lucifer yellow; C007740:fluorexon