Biomacromolecules have transformed our ability to effectively treat disease. 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 facilitate both localization and permeation to achieve systemic drug uptake. Inspired by the leopard tortoise’s ability to passively self-orient, we developed the Self-Orienting Millimeter-scale Applicator (SOMA), an ingestible device that autonomously positions itself to engage with GI tissue. Once in place, it deploys milliposts fabricated from active pharmaceutical ingredients directly through the gastric mucosa while avoiding perforation.

We conducted in vivo studies in rats and swine to evaluate the applicator’s safety and, using insulin as a model drug, demonstrated that the SOMA achieves plasma levels of active pharmaceutical ingredient comparable to those obtained with subcutaneous millipost administration.