title: Skin electroporation: rapid measurements of the transdermal voltage and flux of four fluorescent molecules show a transition to large fluxes near 50 V.
abstract: 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.
authors.affiliation: Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA. tanichen@mit.edu
authors.forename: T
authors.initials: T
authors.lastname: Chen
authors.forename: E M
authors.initials: EM
authors.lastname: Segall
authors.forename: R
authors.initials: R
authors.lastname: Langer
authors.forename: J C
authors.initials: JC
authors.lastname: Weaver
mesh_terms: 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
chemical_list: D005452:Fluoresceins; D005456:Fluorescent Dyes; D007546:Isoquinolines; D009942:Organometallic Compounds; D009943:Organophosphorus Compounds; C066850:Cascade Blue; C017475:lucifer yellow; C007740:fluorexon