Biomacromolecules have transformed our capacity to effectively treat diseases; however, their rapid degradation and poor absorption in the gastrointestinal (GI) tract generally limit their administration to parenteral routes. An oral biologic delivery system must aid in both localization and permeation to achieve systemic drug uptake. Inspired by the leopard tortoise’s ability to passively reorient, we developed an ingestible self-orienting millimeter-scale applicator (SOMA) that autonomously positions itself to engage with GI tissue. It then deploys milliposts fabricated from active pharmaceutical ingredients directly through the gastric mucosa while avoiding perforation. We conducted in vivo studies in rats and swine that support the applicator’s safety and, using insulin as a model drug, demonstrated that the SOMA delivers active pharmaceutical ingredient plasma levels comparable to those achieved with subcutaneous millipost administration.

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Ingestible electronic devices enable noninvasive evaluation and diagnosis of pathologies in the gastrointestinal (GI) tract but generally cannot therapeutically interact with the tissue wall. Here, we report the development of an orally administered electrical stimulation device characterized in ex vivo human tissue and in in vivo swine models, which transiently anchored itself to the stomach by autonomously inserting electrically conductive, hooked probes. The probes provided stimulation to the tissue via timed electrical pulses that could be used as a treatment for gastric motility disorders. To demonstrate interaction with stomach muscle tissue, we used the electrical stimulation to induce acute muscular contractions. Pulses conductively signaled the probes’ successful anchoring and detachment events to a parenterally placed device. The ability to anchor into and electrically interact with targeted GI tissues controlled by the enteric nervous system introduces opportunities to treat a multitude of associated pathologies.

Formulation in nanogels could be a viable approach to improve the safety profile of host defence peptides.