ABSTRACT
Electroporation is an electric enhancement technique that involves application of high-voltage pulses for very short durations of time. While iontophoresis (see Chapter 4) involves the use of relatively low transdermal voltages (typically less than 20 V), electroporation of skin takes place at high transdermal voltages (about 100 V or more). Iontophoresis enhances šux by acting primarily on the drug, and electroporation acts on the skin with some driving force on the drug during a pulse (1). However, iontophoresis will have secondary effects on the skin just like electroporation would apply direct electromotive force on the drug during the brief pulse period. This may be particularly true for the thin cell lining of the sweat ducts which might be electroporated with low voltages of the order used in iontophoresis. Electroporation can expand the scope of iontophoresis to deliver peptides in greater quantities or enable delivery of larger molecules than what can be delivered by iontophoresis. Electroporation, sometimes also termed electropermeabilization, refers to the dramatic changes observed in cell membranes or arti•cial planar bilayer membranes upon application of large transmembrane voltages. These changes involve structural rearrangement and conductance changes leading to temporary loss of semipermeability of cell membranes, and the observations are consistent with the formation of pores. This technique is best known as a physical transfection method in which cells are exposed to a brief electrical pulse, thereby opening pores in the cell membrane, allowing DNA or other macromolecules to enter the cell (2,3). During this process, the transmembrane potential produces a current that passes through the membrane defects and leads to a reversible increase in its permeability by the formation of aqueous pathways that are straight-through with radii of a few nanometers; this process is more energetically favorable than long, tortuous pathways around corneocytes. Even though the exact mechanism for electroporation is not clear, the pore mechanism is generally believed to be the case (4), as changes in the behavior of membranes seen following electroporation are consistent with the theory of pore formation. These include changes in electrical behavior (e.g., changes in membrane conductance are often dramatic and are believed to be due to ionic conduction through transient aqueous pores). However, these pores have not been visualized by any microscopic techniques, presumably due to factors such as their small size and transient nature. Electroporation is considered to be a nonthermal phenomena because pore formation occurs by membrane rearrangement much before any signi•cant temperature rise takes place in the pulsing medium (5).
