Nanoneedle-Based Transdermal Gene Delivery: A Minimally Invasive Strategy for Gene Therapy.

Transdermal drug delivery systems have recently been explored as an alternative to oral systems, which have many challenges. Due to the limitations of first-generation transdermal systems, second- and third-generation systems have been developed, among which microneedles have been the most remarkable products. Building on the advancements of nanotechnology, nanoneedles have recently been developed. Gene therapy molecules-such as DNA, RNA, siRNA, miRNA, and other nucleic acids-are typically delivered using viral or chemical carriers, but these methods face several challenges. In this context, nanoneedles offer a promising and efficient solution for delivering these large molecules. Nanoneedles are a biocompatible and reliable physical method for gene delivery, enabling transdermal administration by penetrating the skin barrier and delivering nucleic acids directly into cells. Their ability to penetrate cellular barriers with minimal invasiveness makes them advantageous for delivering genetic materials. This review will focus on the potential applications of nanoneedles in pharmaceutical contexts, especially in gene therapy. In addition, information on the properties, structure, and fabrication of nanoneedles is also provided.