Oral drug delivery of proteins is limited by the degradative environment of the gastrointestinal tract and poor absorption, requiring parenteral administration of these drugs. Luminal mucus represents the initial steric and dynamic barrier to absorption. To overcome this barrier, we report the development of the RoboCap, an orally ingestible, robotic drug delivery capsule that locally clears the mucus layer, enhances luminal mixing, and topically deposits the drug payload in the small intestine to enhance drug absorption. RoboCap’s mucus-clearing and churning movements are facilitated by an internal motor and by surface features that interact with small intestinal plicae circulares, villi, and mucus. Vancomycin (1.4 kilodaltons of glycopeptide) and insulin (5.8 kilodaltons of peptide) delivery mediated by RoboCap resulted in enhanced bioavailability 20- to 40-fold greater in ex vivo and in vivo swine models when compared with standard oral delivery ( P  < 0.05). Further, insulin delivery via the RoboCap resulted in therapeutic hypoglycemia, supporting its potential to facilitate oral delivery of drugs that are normally precluded by absorption limitations.

The surface mucosa that lines many of our organs houses myriad biometric signals and, therefore, has great potential as a sensor–tissue interface for high-fidelity and long-term biosensing. However, progress is still nascent for mucosa-interfacing electronics owing to challenges with establishing robust sensor–tissue interfaces; device localization, retention and removal; and power and data transfer. This is in sharp contrast to the rapidly advancing field of skin-interfacing electronics, which are replacing traditional hospital visits with minimally invasive, real-time, continuous and untethered biosensing. This Review aims to bridge the gap between skin-interfacing electronics and mucosa-interfacing electronics systems through a comparison of the properties and functions of the skin and internal mucosal surfaces. The major physiological signals accessible through mucosa-lined organs are surveyed and design considerations for the next generation of mucosa-interfacing electronics are outlined based on state-of-the-art developments in bio-integrated electronics. With this Review, we aim to inspire hardware solutions that can serve as a foundation for developing personalized biosensing from the mucosa, a relatively uncharted field with great scientific and clinical potential.