An ingestible self-orienting system for oral delivery of macromolecules

Delivering fragile drugs to the gut Oral delivery is the simplest and least invasive way to deliver many pharmaceuticals, but many drugs and medications, including insulin, cannot survive passage through the stomach or the gastrointestinal tract. Abramson et al. developed an ingestible delivery vehicle that could self-reorient from any starting position so as to attach to the gastric wall. Encapsulation of a spring in a sugar casing allowed for triggered actuation for the delivery of biomolecules. The approach successfully provided active insulin delivery in pigs. Science, this issue p. 611 An oral device efficiently delivers biomacromolecules via gastric injection. 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.