Radiofrequency-driven skin microchanneling as a new way for electrically assisted transdermal delivery of hydrophilic drugs

Amnon C. Sintov, Igor Krymberk, Dorit Daniel, Talli Hannan, Ze'ev Sohn, Galit Levin

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    122 Scopus citations


    The aim of this study was to increase the skin penetration of two drugs, granisetron hydrochloride and diclofenac sodium, using a microelectronic device based on an ablation of outer layers of skin using radiofrequency high-voltage currents. These radiofrequency currents created an array of microchannels across the stratum corneum deep into the epidermis. The percutaneous penetration studies were first performed in vitro using excised full thickness porcine ear skin. An array of 100 microelectrodes/cm2 was used in these studies. The skin permeability of both molecules was significantly enhanced after pretreatment with the radiofrequency microelectrodes, as compared to the delivery through the untreated control skin. Steady state fluxes of 41.6 μg/cm2/h (r=0.997) and 23.0 μg/cm2/h (r=0.989) were obtained for granisetron and diclofenac, respectively. The enhanced transdermal delivery was also demonstrated in vivo in rats. It was shown that diclofenac plasma levels in the pretreated rats reached plateau levels of 1.22±0.32 μg/ml after 3 h to 1.47±0.33 μg/ml after 6 h, as compared to 0.16±0.04 μg/ml levels obtained after 6 h in untreated rats. Similarly, application of granisetron patches (3% in crosslinked hydrogel) onto rats' abdominal skin pretreated with radiofrequency electrodes resulted in an averaged peak plasma level of 239.3±43.7 ng/ml after 12 h, which was about 30 times higher than the plasma levels obtained by 24-h passive diffusion of the applied drug. The results emphasize, therefore, that the new transdermal technology is suitable for therapeutic delivery of poorly penetrating molecules.

    Original languageEnglish
    Pages (from-to)311-320
    Number of pages10
    JournalJournal of Controlled Release
    Issue number2
    StatePublished - 29 Apr 2003


    • Diclofenac
    • Granisetron
    • Radiofrequency ablation
    • Radiofrequency-microchannels
    • Skin permeation
    • Transdermal delivery


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