Creation of transdermal pathways for macromolecule transport by skin electroporation and a low toxicity, pathway-enlarging molecule

A combined electrical (HV, “high voltage”, pulsing) and chemical (topical sodium thiosulfate) intervention is hypothesized to create enlarged aqueous pathways that allow large quantities of macromolecules to be transported through human skin's stratum corneum (SC), the dominant barrier for transdermal drug delivery and biochemical analyte extraction. This expectation is based on the known structure and composition of the SC, and previous models and experiments for local transport regions (LTRs) due to transdermal HV pulsing. In vitro experiments demonstrated that transdermal macromolecule fluxes of 10⁻⁹ to 10⁻⁸ mol h⁻¹ cm⁻² (10 to 100 μg h⁻¹ cm⁻²) or greater are possible for lactalbumin and an antibody (IgG), which are potentially therapeutic values for peptides, proteins and nucleic acids. In the absence of sodium thiosulfate, only a small molecule (sulforhodamine) flux increased significantly, consistent with many previous studies. Significant macromolecule transdermal fluxes occurred only if a pathway enlarging molecule (sodium thiosulfate) was present. Our results also provide support for the mechanism hypothesis that HV pulses leading to transdermal voltages U_skin>50 V create straight-through aqueous pathways that penetrate multilamellar bilayer membranes, corneocyte envelopes and corneocyte interiors within the SC.