In vivo efficacy and safety of skin electroporation

This article reviews the studies on skin electroporation carried out in viv o in animals and emphasizes its potential therapeutic applications for tran sdermal and topical drug delivery. In agreement with in vitro studies, tran sport across skin due to high-voltage pulses in vivo was shown to increase by orders of magnitude on a timescale of minutes. Increased transdermal tra nsport was measured by systemic blood uptake and/or pharmacological respons e, and demonstrated for calcein, a fluorescent tracer, fentanyl, a potent a nalgesic and flurbiprofen, an antiinflammatory drug. Combined electroporati on with iontophoresis was shown to provide rapidly responsive transdermal t ransport of luteinizing hormone releasing hormone ex vivo as well. These da ta underline the potential of skin electroporation for improving the delive ry profile of existing conventional transdermal patches, but also for repla cing the injectable route. High-voltage pulses can increase drug permeation within and across skin but are also an efficient tool to permeabilize the membrane of cells of the cu taneous or subcutaneous tissue. This was shown beneficial for targeting cut aneous cells with oligonucleotides or genes and might open new opportunitie s for gene therapy and DNA vaccination. The safety of the application of high-voltage pulses on skin was assessed i n vivo, using histological and visual scores, and bioengineering methods. W hile changes in skin barrier and function were observed, the irritation was mild and short-lived. Further optimization of the electrode configuration for improved targeting of the stratum corneum should still improve toleranc e and levels of sensation. (C) 1999 Elsevier Science BN. All rights reserve d.