The delivery of macromolecules via the gastrointestinal (GI) tract remains a significant challenge. A variety of technologies using physical modes of drug delivery have been developed and investigated to overcome the epithelial cell layer of the GI tract for local and systemic delivery. These technologies include direct injection, jetting, ultrasound, and iontophoresis, which have been largely adapted from transdermal drug delivery. Direct injection of agents using needles through endoscopy has been used clinically for over a century. Jetting, a needle-less method of drug delivery where a high-speed stream of fluid medication penetrates tissue, has been evaluated pre-clinically for delivery of agents into the buccal mucosa. Ultrasound has been shown to be beneficial in enhancing delivery of macromolecules, including nucleic acids, in pre-clinical animal models. The application of an electric field gradient to drive drugs into tissues through the technique of iontophoresis has been shown to deliver highly toxic chemotherapies into GI tissues. Here in, we provide an in-depth overview of these physical modes of drug delivery in the GI tract and their clinical and preclinical uses.

通过胃肠道 (GI) 输送大分子仍然是一项重大挑战。已经开发和研究了多种使用药物递送物理模式的技术，以克服胃肠道的上皮细胞层进行局部和全身递送。这些技术包括直接注射、喷射、超声和离子电渗疗法，这些技术在很大程度上改编自透皮给药。通过内窥镜使用针头直接注射药剂已在临床上使用了一个多世纪。喷射是一种无针药物输送方法，其中高速流体药物流穿透组织，已在临床前评估用于将药剂输送到颊粘膜。超声已被证明有利于增强包括核酸在内的大分子的递送，在临床前动物模型中。通过离子电渗技术应用电场梯度将药物驱动到组织中已被证明可以将剧毒的化学疗法传递到 GI 组织中。在这里，我们深入概述了这些在胃肠道中药物输送的物理模式及其临床和临床前用途。