压电微针电穿孔器在人体中的耐受性

IF 6.1 2区 医学 Q1 ENGINEERING, BIOMEDICAL Bioengineering & Translational Medicine Pub Date : 2024-03-14 DOI:10.1002/btm2.10662
Chao-Yi Lu, Pankaj Rohilla, Eric I. Felner, Gaurav Byagathvalli, Erkan Azizoglu, M. Saad Bhamla, Mark R. Prausnitz
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引用次数: 0

摘要

电穿孔,即使用电脉冲促进 DNA、RNA 和其他分子的细胞内输送,是一种成熟的技术,已被证明可显著增强 DNA/mRNA 疫苗和疗法的免疫原性。然而,由于成本高、体积大、用户操作复杂以及神经刺激对人体的耐受性差等原因,传统电穿孔器的临床应用一直受到限制。在之前的工作中,我们介绍了 ePatch:一种超低成本、手持式、无电池的电穿孔器,采用压电脉冲器与微针电极阵列相结合,在小鼠皮内注射 SARS-CoV-2 DNA 疫苗后显示出增强的免疫原性反应。目前的研究将重点从疗效转移到了耐受性上,假设 ePatch 的微针阵列能将电场定位到皮肤浅层,从而最大限度地减少对神经的刺激,提高患者的舒适度。我们在 14 名健康成年人身上测试了这一假设,并监测了电穿孔带来的疼痛和其他潜在不良反应。与传统的皮下注射针相比,ePatch 的疼痛感更小。施用 ePatch 时,施用部位的疼痛、触痛、红斑和肿胀等不良反应极小,而且是一过性的,施用实验用 ePatch 与施用安慰剂在统计学上没有区别,这表明电穿孔具有极佳的耐受性。总之,ePatch 在人体中具有良好的耐受性,有望在各种临床环境中安全使用电穿孔,包括 DNA 和 mRNA 疫苗接种。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

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Tolerability of a piezoelectric microneedle electroporator in human subjects

Electroporation, or the use of electric pulses to facilitate the intracellular delivery of DNA, RNA, and other molecules, is a well-established technique, that has been demonstrated to significantly augment the immunogenicity of DNA/mRNA vaccines and therapeutics. However, the clinical translation of traditional electroporators has been limited due to high costs, large size, complex user operation, and poor tolerability in humans due to nerve stimulation. In prior work, we introduced ePatch: an ultra-low-cost, handheld, battery-free electroporator employing a piezoelectric pulser coupled with a microneedle electrode array that showed enhanced immunogenic responses to an intradermal SARS-CoV-2 DNA vaccine in mice. The current study shifts focus from efficacy to tolerability, hypothesizing that ePatch's microneedle array, which localizes the electric field to the superficial skin strata, will minimize nerve stimulation and improve patient comfort. We tested this hypothesis in 14 healthy adults, monitoring pain and other potential adverse effects associated with electroporation. Compared to the insertion of a traditional hypodermic needle, the ePatch was less painful. Adverse effects such as pain, tenderness, erythema and swelling at the application sites were minimal, transient, and statistically indistinguishable between the experimental and placebo ePatch application, suggesting excellent tolerability towards electroporation. In summary, ePatch has a favorable tolerability profile in humans and offers the potential for the safe use of electroporation in a variety of clinical settings, including DNA and mRNA vaccination.

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来源期刊
Bioengineering & Translational Medicine
Bioengineering & Translational Medicine Pharmacology, Toxicology and Pharmaceutics-Pharmaceutical Science
CiteScore
8.40
自引率
4.10%
发文量
150
审稿时长
12 weeks
期刊介绍: Bioengineering & Translational Medicine, an official, peer-reviewed online open-access journal of the American Institute of Chemical Engineers (AIChE) and the Society for Biological Engineering (SBE), focuses on how chemical and biological engineering approaches drive innovative technologies and solutions that impact clinical practice and commercial healthcare products.
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