Permeabilization of human stratum corneum and full-thickness skin samples by a direct dielectric barrier discharge

Purpose

The tight barrier formed by human stratum corneum (SC) has a significantly protective function but also prevents the delivery of drug substances through the skin. In order to permeabilize the SC for drug delivery we use cold atmospheric plasma (CAP).

Methods

A direct ex vivo treatment of human skin with cold atmospheric plasma, specifically a dielectric barrier discharge (DBD) using skin as the ground electrode, was employed to permeabilize the stratum corneum (SC) throughout a treated area of 0.5 cm². The permeabilization of isolated SC and full-thickness skin was evaluated through changes in transepithelial electrical resistance. Franz diffusion cell permeation using differently sized hydrophilic particles enabled an estimation of the pore size and drug transport efficiency. Furthermore, silver sheet oxidation showed the distribution of local permeabilized regions.

Results

The transepithelial electrical resistance showed a long-term overall drop for treatments ≥90 s in isolated SC as well as full-thickness skin. Silver sheet oxidation revealed a regular pattern of local permeabilized regions greater in number than the expected number of skin appendages in treated isolated human SC. Permeation study results indicate that relatively small hydrophilic substances with Stokes’ radii up to 1.4 nm are efficiently transported through human SC subsequent to 2×90 s treatment with direct cold atmospheric plasma at a power density of about 0.2 W cm⁻². A moderate permeation of particles up to 6 μm in diameter is evident for the occasional formation of large pores in the μm-range. Finally, a mechanism for DBD plasma permeabilization of skin is proposed and discussed.