Mechanistic view of skin electroporation – models and dosimetry for successful applications: an expert review

Introduction Skin electroporation is a promising treatment for transdermal drug delivery, gene electrotransfer, skin rejuvenation, electrochemotherapy, and wound disinfection. Although a considerable amount of in vitro and in vivo studies exists, the translation to clinics is not as fast as one would hope. We hypothesize the reason lies in the inadequate dosimetry, i.e. electrode configurations, pulse parameters, and pulse generators used. We suggest adequate dosimetry can be determined by mathematical modeling which would allow comparison of protocols and facilitate translation into clinics.Areas covered We introduce the mechanisms and applications of skin electroporation, present existing mathematical models and compare the influence of different model parameters. We review electrodes and pulse generators, prototypes, as well as commercially available models.Expert opinion The reasons for slow translation of skin electroporation treatments into clinics lie in uncontrolled and inadequate dosimetry, poor reporting rendering comparisons between studies difficult, and significant differences in animal and human skin morphology often dismissed in reports. Mathematical models enable comparison of studies, however, when the parameters of the pulses and electrode configuration are not adequately reported, as is often the case, comparisons are difficult, if not impossible. For each skin electroporation treatment, systematic studies determining optimal parameters should be performed and treatment parameters standardized.