(F-232) A piezoelectric microneedle electroporator for simplified DNA and RNA delivery: a tolerability study in human subjects

Introduction:: Electroporation is used extensively in the laboratory to increase cellular uptake of DNA, RNA, and other types of molecules, and has been shown to facilitate targeted cancer treatments and to enhance immunogenicity of DNA and mRNA vaccines in preclinical and clinical studies. However, commercially available electroporators are typically bulky ( >5 kg) and expensive (thousands of dollars) and cause significant nerve stimulation during high-voltage pulsing, which can limit the widespread use of electroporation for medical applications. Our lab has developed a handheld, battery-free electroporation device (i.e., ePatch) that consists of a piezoelectric pulser and microneedle electrode array, which costs less than $1 and has been shown to increase the immunogenicity of a SARS-CoV-2 DNA vaccine¹. Because ePatch uses microneedle electrodes that penetrate just a few hundred microns into the skin, we hypothesize that the electroporation pulses will minimize nerve stimulation and provide improved tolerability in human subjects.


Materials and Methods:: In this study, 13 healthy adults were recruited, and each blind to the five randomized procedures they received: (1) ePatch with no pulse (placebo), (2) ePatch with 10 disconnected pulses (placebo), (3) ePatch with 1 pulse, (4) ePatch with 10 pulses, and (5) a 25G 5/8” hypodermic control. Participants rated their pain during administration using a visual analog scale. Following administration, investigators evaluated pain, tenderness, erythema, and swelling using a standardized score sheet.


Results, Conclusions, and Discussions:: Participants rated all four of the ePatch experimental and placebo as less painful than the hypodermic needle control (Fig. 1). When comparing pain scores between the ePatch experimental groups (using 1 or 10 pulses) to the ePatch control groups (using no pulse or 10 disconnected pulses), no significant difference (p< 0.05) was observed among the groups, except between the ePatch with 10 disconnected pulses and ePatch with 10 pulses (Fig. 1).



When considering pain, tenderness, erythema, and swelling after the treatments, there was no significant difference between the experimental and the placebo ePatch groups. Pain, tenderness, and swelling scores were mostly zero, and any erythema was typically mild and transient (Fig. 2), dissipating by the time of the following day's examination.


These findings suggest that the piezoelectric microneedle electroporator is well-tolerated. The skin's response to the ePatch, regardless of pulse application, appears to be at least as well-tolerated as the response to conventional hypodermic needle insertion.


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References (Optional): : ¹ Xia, D., Jin, R., Byagathvalli, G., Yu, H., Ye, L., Lu, C.-Y., Bhamla, M. S., Yang, C., and Prausnitz, M. R. (2021). An ultra-low-cost electroporator with microneedle electrodes (ePatch) for SARS-CoV-2 vaccination. Proceedings of the National Academy of Sciences, 118(45):e2110817118.