A self-triggering and fully sustainable gastric device enabling long-acting oral delivery of macromolecules

Long-acting oral delivery of macromolecular therapeutics remains difficult, as most oral delivery devices focus on improving gastrointestinal absorption but do not adequately address sustained drug release and frequent dosing. In parallel, many gastric-retentive systems rely on nondegradable structural components, raising concerns regarding retained-device burden and postuse medical waste. Here, we report a biodegradable oral capsule device for long-lasting drug delivery, termed the sustainable gastric self-triggered device (SGSTD), inspired by the stinging mechanism of Apis mellifera . After reaching the stomach, SGSTD autonomously deploys a biodegradable barbed drug-loaded needle into the gastric wall, while the remaining carrier body is subsequently excreted, establishing a bioinspired “deploy-and-separate” strategy for long-acting gastric delivery. The embedded needle enables microchannel-mediated sustained release, with structurally tunable release behavior. Ex vivo and in vivo porcine studies confirmed gastric deployment, tissue retention, systemic safety, and localized tissue repair around the insertion region. In vivo, SGSTD maintained insulin delivery for over 7 days, achieving a relative bioavailability of 63.8%, approximately 17.2-fold higher than conventional oral administration. SGSTD is cost-effective, scalable, and composed of biodegradable materials, providing a sustainable strategy for long-acting oral biologics delivery.