Spatially constrained skin electroporation with sodium thiosulfate and urea creates transdermal microconduits

Abstract

Controlled transport of molecules through the skin’s main barrier, the stratum corneum (SC), is a long standing goal of transdermal drug delivery. Traditional, needle-based injection provides delivery of almost any water soluble compound, by creating a single large aqueous pathway in the form of the hollow core of a needle, through which drug is delivered by pressure-driven flow. We extend previous work to show that SC-spanning microconduits (here with diameters of about 200 μm) can be created in vivo by skin electroporation and low-toxicity, keratolytic molecules (here sodium thiosulfate and urea). A single microconduit in isolated SC can support volumetric flow of the order of 0.01 ml s−1 by a pressure difference of only 0.01 atm (about 102 Pa), demonstrating that the SC barrier has been essentially eliminated within this microscopic area.