Bioinspired, ingestible electroceutical capsules for hunger-regulating hormone modulation.

The gut-brain axis, which is mediated via enteric and central neurohormonal signaling, is known to regulate a broad set of physiological functions from feeding to emotional behavior. Various pharmaceuticals and surgical interventions, such as motility agents and bariatric surgery, are used to modulate this axis. Such approaches, however, are associated with off-target effects or post-procedure recovery time and expose patients to substantial risks. Electrical stimulation has also been used to attempt to modulate the gut-brain axis with greater spatial and temporal resolution. Electrical stimulation of the gastrointestinal (GI) tract, however, has generally required invasive intervention for electrode placement on serosal tissue. Stimulating mucosal tissue remains challenging because of the presence of gastric and intestinal fluid, which can influence the effectiveness of local luminal stimulation. Here, we report the development of a bioinspired ingestible fluid-wicking capsule for active stimulation and hormone modulation (FLASH) capable of rapidly wicking fluid and locally stimulating mucosal tissue, resulting in systemic modulation of an orexigenic GI hormone. Drawing inspiration from Moloch horridus, the "thorny devil" lizard with water-wicking skin, we developed a capsule surface capable of displacing fluid. We characterized the stimulation parameters for modulation of various GI hormones in a porcine model and applied these parameters to an ingestible capsule system. FLASH can be orally administered to modulate GI hormones and is safely excreted with no adverse effects in porcine models. We anticipate that this device could be used to treat metabolic, GI, and neuropsychiatric disorders noninvasively with minimal off-target effects.

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.