A Programmable Oral Nanomotor Microcapsule for the Treatment of Inflammatory Bowel Disease

Abstract Given the unique anatomy and location of inflammatory bowel disease (IBD), oral pharmacological treatment is the mainstay for managing IBD because of its convenience and direct accessibility to the gastrointestinal tract. However, efficient delivery systems must be designed to navigate the harsh gastrointestinal environment during application. Here, an innovative oral drug delivery system was proposed using nanomotor (NM)‐loaded soluble microcapsules for treating IBD. MnO 2 ‐Au‐mSiO 2 NMs incorporate partially encapsulated MnO 2 antennas that convert reactive oxygen species into oxygen, autonomously propelling the NMs. Astaxanthin (AST), known for its anti‐inflammatory properties, is loaded into the mesoporous silica (mSiO 2 ) of NMs (AST@NMs). AST effectively reduces inflammation and shifts macrophages from a proinflammatory (M1) phenotype to an anti‐inflammatory (M2) phenotype. To protect the nanomotors from harsh digestive conditions and achieve intestinal‐responsive release, using photocurable 3D printing, we fabricated enteric‐coated oral microcapsules (MCs). Additionally, to prevent leakage of AST@NMs, a calcium alginate shell was cured in situ on the surface of the microcapsules (AST@NMs@MCs). In vitro and in vivo, AST@NMs@MCs effectively reduced inflammation, repaired the intestinal barrier, and modulated the gut microbiota. These findings underscore the protective effects of the microcapsules on AST@NM, highlighting their potential as a promising strategy for treating colitis.