Optimization of a plasma facilitated DNA delivery method

Plasma-based methods have recently emerged as a technique for augmenting plasmid DNA delivery to skin. This delivery modality relies on the deposition of ionized gas molecules on to targeted cells or tissue to establish an electric field. It is hypothesized that this electric field results in the dielectric breakdown of cell membranes, making cells permeable to exogenous molecules. This in vivo investigation sought to optimize the intradermal delivery of a luciferase expressing plasmid DNA by modulating the total exposure to the plasma source and the plasmid DNA dose. Varying the plasma exposure time from 2, 5, 10, and 20min allowed the conditions resulting in the highest expression of luciferase to be found. These conditions correlated to the 10minute exposure time for a plasma derived from either +8kV or −8kV, when the generator was operated 3cm from the epidermal tissue surface with a helium flow rate of 15L/min. Exposing the injected flank skin for 10min resulted in a rise of 37.3-fold for a plasma created with +8kV and 27.1-fold for a plasma created with −8kV. When using this treatment time with 50, 100, or 200μg of a luciferase expressing plasmid, it was found that 100μg resulted in the highest peak luminescence. •Plasma deposition on the epidermal skin surface is capable of augmenting uptake of intradermally injected plasmid DNA.•A dose-response relationship between plasma exposure and plasmid DNA expression was observed in the bioluminescence data.•Maximum expression was observed when 100μg of plasmid DNA was treated with a 10min plasma discharge.•Results obtained with the plasma-based delivery system were similar to those obtained with electroporation.