Multipulse Generators for Electroporation-Mediated Intradermal Delivery of Nucleic Acids

Electroporation-mediated delivery can provide a safer and better alternative to carrier-based platforms for intracellular delivery of nucleic acids. Electroporation overcomes the issues of stability, immunogenicity, and toxicity of lipid nanoparticles and viral vectors through direct physical membrane permeabilization. However, conventional electroporators are expensive, bulky, non-portable, and cause painful administration. An ultra-low-cost, piezoelectric-based electroporation device (ePatch) has demonstrated enhanced intradermal delivery of mRNA and plasmid DNA in rodents. Electroporation via an ePatch facilitated enhanced gene/protein expression and elicited strong immune responses against SARS-CoV-2 using both mRNA and plasmid-based COVID-19 vaccines. Administration of 3 to 10 electric pulses via an ePatch also provided greater cellular uptake of nucleic acids compared to a single electric pulse.

The manual triggering of ePatch can cause delivery inconsistencies from user fatigue, variable pulse timing, and inconsistent applied pressure on skin. To address these limitations and improve clinical usability, we developed the RotoPatch family of electroporators, which use a single rotary motion to administer multiple electroporation pulses to skin through microneedle electrode arrays (MEA). To assess performance, we characterized the voltage profiles of the ePatch, the manual RotoPatch, and the eIgniter (battery-powered RotoPatch with no moving parts), in open circuit and in ex-vivo porcine skin.

In this poster, we will present data on electrical characterization of pulsing, which revealed that the ePatch and RotoPatch produced nominal electric fields strengths within the acceptable range for electroporation (1 – 4 kV/cm) at 2.8 kV/cm and 3.6 kV/cm, whereas the eIgniter produced a value of 7.2 kV/cm in ex-vivo porcine skin. These values are comparable to other conventional electroporators such as BTX AgilePulse (0.25 – 5 kV/cm), Cliniporator (1.3 – 10 kV/cm), and Cellectra (0.13 - 0.67 kV/cm). We also found the eIgniter produced the highest peak currents (3.67 ± 0.07 A, and −2.97 ± 0.09 A), followed by ePatch (2.78 ± 0.86 A and −2.36 ± 0.36 A), and RotoPatch (2.02 ± 1.87 A and −2.11 ± 0.29 A). Furthermore, our team showed that the RotoPatch electroporators enhanced the protein and gene expression of mRNA and plasmid DNA in mice and rats, respectively.

RotoPatch electroporators offers flexibility for clinical settings, with the motorized version facilitating ease of use for providers, while the manual version being better-suited for resource-limited environments. The use of widely available piezoelectric and electrical components, such as those found in barbeque lighters, also highlight the potential for rapid, global scalability of these electroporation devices for vaccination. Our findings thus show that low-cost, handheld RotoPatch electroporators offer a scalable, carrier-free method of intradermal delivery of mRNA and DNA.