MACROMOLECULES AS NOVEL TRANSDERMAL TRANSPORT ENHANCERS FOR SKIN ELECTROPORATION

Purpose. Macromolecules were investigated as chemical enhancers of tra nsdermal transport by skin electroporation. Although unable to enhance passive or iontophoretic transport, macromolecules are proposed to en hance electroporation-assisted delivery by stabilizing the increased p ermeability caused by high-voltage pulses. Methods. To test this hypot hesis, we examined the timescale of transport, the influence of electr ical protocol and the influence of macromolecule size, structure, and charge on enhancement of transdermal mannitol transport in vitro by he parin, dextran-sulfate, neutral dextran, and poly-lysine. Results. Ski n electroporation increased transdermal mannitol delivery by approxima tely two orders of magnitude. The addition of macromolecules further i ncreased transport up to five-fold, in support of the proposed hypothe sis. Macromolecules present during pulsing enhanced mannitol transport after pulsing for hours, apparently by a macromolecule-skin interacti on. No enhancement was observed during passive diffusion or low-voltag e iontophoresis, suggesting that macromolecules interact specifically with transport pathways created at high voltage. Although all macromol ecules studied enhanced transport, those with greater charge and size were more effective. Conclusions. This study demonstrates that macromo lecules can be used as trandermal transport enhancers uniquely suited to skin electroporation.