Transdermal drug delivery by skin electroporation in the rat

Drug delivery across skin offers advantages over conventional modes of administration. It avoids gastrointestinal degradation and the hepatic first-pass effect, has potential for controlled and sustained delivery, is user-friendly and therefore improves patient compliance (1-2). However, because the skin's outer layer, the stratum corneum, is an extremely effective barrier, transdermal transport of most drugs is very slow, exhibits lag times of hours and steadystate rates that are often subtherapeutic. Chemical and physical approaches to increasing transdermal transport have been explored. Recently, the intermittent application of short (e.g., milliseconds), high-voltage (e.g., 100 V across skin) pulses has been shown to increase transport across skin by several orders of magnitude on a time scale of minutes, probably by a mechanism involving electroporation (3-6).