Macromolecules as Novel Transdermal Transport Enhancers for Skin Electroporation

Abstract

Drug delivery across skin offers a noninvasive, user-friendly alternative to conventional oral or injected administration^l. However, skin is an extremely effective barrier which prevents transport of most drugs at therapeutic rates. Recently, electroporation² of skin using short (e.g., ms), high-voltage (e.g., 100 V) pulses has been shown to increase transdermal transport by many orders of magnitude^3,4. In this study, we hypothesized that macromolecules, although not expected to enhance passive transport, could enhance electroporation-assisted delivery by stabilizing the increased permeability caused by high-voltage pulses. Previous work suggested that DNA could stabilize electropermeabilization of cell membranes⁵ and heparin might stabilize electropermeabilization of skin⁶ possibly by being inserted into “electropores” and hindering their closure⁷.