Scientists built tiny, layered beads that can survive the stomach’s harsh acid and then release anti‑inflammatory compounds like the peptide KPV right where they’re needed in the colon. The beads keep KPV active and help it work on gut cells that repair the lining.

Although oral delivery of therapeutic agents offers numerous benefits, its application is limited due to the digestive tract's harsh conditions (e.g., strong acidity and high osmolarity), which impair activity and create challenges in achieving targeted release into the intestine. Here, we present multicompartmental hydrogel microspheres equipped with a concentric oil layer to significantly enhance the oral drug delivery efficiency for treating inflammatory bowel disease (IBD). These microspheres are created through the utilization of triple-emulsion droplets, featuring intermediate oil layers that distinctively separate two prepolymer phases, allowing us to fine-tune the composition of each compartment through a tailored polymerization strategy. We demonstrate that the oil layer can protect the encapsulated material by preventing exposure to the acidic environment of the stomach during the digestive process. Unlike aqueous core capsules, the core is composed of hydrogel, which provides high stability even under high osmolarity conditions in the stomach. By fine-tuning the shell's composition, we can develop capsules that release selectively in response to the gut's pH conditions. We demonstrate the system's efficacy by preserving the anti-inflammatory activities of 5-aminosalicylic acid (5-ASA) and Lys-Pro-Val (KPV) under stomach conditions and maintaining their therapeutic effects on colonic epithelial cell migration and proliferation.