Enhancing transdermal delivery of drug-infused particles using electrostatic pulse

Abstract

Transdermal delivery is an ever-increasing field of research because it has many advantages over other methods. Currently, transdermal systems for hormone replacement therapy, smoking cessation, and pain management are common. However, there have been challenges in expanding use of the technology due to difficulty penetrating the skin at the levels or rates that achieve a significant therapeutic effect. Therefore, conventional passive transdermal delivery has been applicable to only small, lipophilic ('lipid or fat loving') substances. Recent research has focused on "needle-free" methods to breach the skin barrier for the purpose of delivering larger molecules and more dose volume. Electroporation is one method typically used to permeabilize a membrane transiently by the application of a single or multiple short electric pulses. This method has been used extensively to permeabilize cells for the purpose of delivering molecules into cells. The application to transdermal delivery, however, is a more recent area of research. Our eventual research goal was to enhance transdermal vaccine delivery by using nanoparticles and an applied voltage pulse to electroporate the skin, followed by interlayer diffusion of the drug-laden nanopatiicles. The approach to developing this delivery method began with initial modeling of the electric fields and their time evolution in each of various layers of the skin. Until very recently, research regarding electroporation of the skin has relied almost exclusively on standard experimental methods without the valuable contribution of an electrostatic-field model upon which to base the experimental work. This analysis assisted us in the selection among the many variables associated with transdermal drug delivery via electroporation: pulse application and parameters, electrode design and placement. Electroporation protocols were explored for the purpose of efficiently and effectively propelling the charged drug-encased nanoparticles in such a way as to enhance movement through the skin while also targeting a specific skin layer. A basic delivery method and parameters were developed to achieve our eventual goal, and the model was tested experimentally with micron particles for validation.