Devices for drug delivery in the gastrointestinal tract: A review of systems physically interacting with the mucosa for enhanced delivery

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.