Frank Reidy Research Center for Bioelectrics, Old Dominion University, Norfolk, VA, 23508, USA.
J Control Release. 2011 May 10;151(3):256-62. doi: 10.1016/j.jconrel.2011.01.014. Epub 2011 Jan 22.
Because of its large surface area and easy access for both delivery and monitoring, the skin is an attractive target for gene therapy for cutaneous diseases, vaccinations and several metabolic disorders. The critical factors for DNA delivery to the skin by electroporation (EP) are effective expression levels and minimal or no tissue damage. Here, we evaluated the non-invasive multielectrode array (MEA) for gene electrotransfer. For these studies we utilized a guinea pig model, which has been shown to have a similar thickness and structure to human skin. Our results demonstrate significantly increased gene expression 2 to 3 logs above injection of plasmid DNA alone over 15 days. Furthermore, gene expression could be enhanced by increasing the size of the treatment area. Transgene-expressing cells were observed exclusively in the epidermal layer of the skin. In contrast to caliper or plate electrodes, skin EP with the MEA greatly reduced muscle twitching and resulted in minimal and completely recoverable skin damage. These results suggest that EP with MEA can be an efficient and non-invasive skin delivery method with less adverse side effects than other EP delivery systems and promising clinical applications.
由于皮肤具有较大的表面积，并且便于给药和监测，因此成为治疗皮肤疾病、疫苗接种和多种代谢紊乱的基因治疗的一个有吸引力的靶标。电穿孔（EP）将 DNA 递送至皮肤的关键因素是有效表达水平和最小或无组织损伤。在这里，我们评估了多电极阵列（MEA）在基因电转移中的应用。对于这些研究，我们利用了豚鼠模型，该模型已被证明与人皮肤具有相似的厚度和结构。我们的结果表明，在 15 天内，与单独注射质粒 DNA 相比，基因表达显著增加了 2 到 3 个对数级。此外，通过增加处理面积还可以增强基因表达。转染细胞仅观察到在皮肤的表皮层中。与测微计或板电极相比，MEA 的皮肤 EP 大大减少了肌肉抽搐，并且导致最小和完全可恢复的皮肤损伤。这些结果表明，MEA 的 EP 可以是一种有效且非侵入性的皮肤递药方法，其与其他 EP 递药系统相比副作用更少，具有广阔的临床应用前景。
