Non-invasive nanosecond electroporation for biocontrol of surface infections: an in vivo study

Abstract

Invasive infections caused by drug-resistant bacteria are frequently responsible for fatal sepsis, morbidity and mortality rates. In this work, we propose a new methodology based on nanosecond high frequency electric field bursts, which enables successful eradication of bacteria in vivo. High frequency (15 kHz) 15–25 kV/cm 300–900 ns pulsing bursts were used separately and in combination with acetic acid (0.1–1%) to treat Pseudomonas aeruginosa in a murine model. Acetic acid 1% alone was effective resulting in almost 10-fold reduction of bacteria viability, however combination of nanosecond electric field and acetic acid 1% treatment was the most successful showing almost full eradication (0.01% survival compared to control) of the bacteria in the contaminated area. The short duration of the pulses (sub-microsecond) and high frequency (kHz range) of the burst enabled reduction of the muscle contractions to barely detectable level while the proposed applicators ensured predominantly topical treatment, without electroporation of deeper tissues. The results of our study have direct application for treatment of wounds and ulcers when chemical treatment is no longer effective.

Doxorubicin Assisted by Microsecond Electroporation Promotes Irreparable Morphological Alternations in Sensitive and Resistant Human Breast Adenocarcinoma Cells

“…The energy levels necessary for the electroporation-supported therapy are similar to the intensities used for ECT in vivo [44]. For the successive clinical electrochemotherapy of human breast cancer with bleomycin, Whelan et al applied pulses of intensity 1400 V/cm, 100 µs duration [45].…”

Research and development of the high-frequency square-wave pulse electroporation system

“…As indicated in Table 3.1, the device was successfully used to investigate the nsPEF effects, which resulted the proposal of new treatment methodologies and non-viral gene delivery methods proof of concept (Novickij, Rembialkowska, et al 2020;Ruzgys et al 2018;Novickij, Zinkevičienė, Perminaitė, et al 2018;Novickij, Stanevičienė, et al 2020;Novickij, Zinkevičienė, Valiulis, et al 2018;Novickij, Zinkevičienė, Stanevičienė, et al 2018;Novickij, Česna, et al 2019), which confirmed, that nsPEF bursts can be used for eradication of bacteria. The developed square-wave systems application has also included the research in MHz pulse repetition frequency range (Ruzgys et al 2019;Pakhomov et al 2019).…”

Low concentrations of acetic and formic acids enhance the inactivation of Staphylococcus aureus and Pseudomonas aeruginosa with pulsed electric fields

“…We believe, that the potential solution to the mentioned problems is to use the topical delivery of acetic acid to serve as a high impedance electrode/tissue interface and deliver the pulses using electrodes without forming a skin lump or keeping it minimal. The difference in load bioimpedances would result in only a thin layer of epidermis being affected, while the depth of ablation could be controlled by the bioimpedance of the electrode/tissue contact and by the amplitude of electric field [65]. In cases of wound treatment, the low penetration depth of PEF is advantageous, since it will allow to sustain the PEF effect predominantly in the infected volume.…”