Rapid temporal control of transdermal drug delivery by electroporation.

Abstract

Transdermal drug delivery has the potential to be a noninvasive. user-friendly method of delivering drugs at steady or time-varying rates ( 1.2). However, to date it has found limited clinical application. largely because transport of most drugs across human skin is very slow, exhibiting lag times of hours to days and steady-state rates which are often subtherapeutic. Recently, evidence for electroporation of skin has been demonstrated and proposed as a mechanism to enhance transdermal drug delivery (3-7). Electroporation involves the application of a brief electric field pulse which creates aqueous pathways in lipid hilayers. such as cell membranes (8-11). During electroporation, the electric field is believed to increase molecular transport dramatically by a combination of two mechanisms: 1) electropores are created and 2) as pores appear, molecules are rapidly moved through the pores by electrophoresis and/ or electroosmosis due to the local field. Electroporation of skin could have significance for drug delivery. having been shown to cause transdermal flux increases up to four orders of magnitude which are largely or fully reversible. possibly involving transient structural changes in the intercellular lipid bilayers of the stratum corneum (5.12). This study focuses on the rapid kinetics of transdermal transport by electroporation, which may allow rapid onset of therapeutic action and/or complex drug delivery profiles during transdermal drug delivery.