In situ fabrication of radiopaque microcapsules for oral delivery and real-time gastrointestinal tracking of Bifidobacterium

Introduction: Although oral administration of Bifidobacterium is a promising approach for diseases, lack of resistance to harsh conditions and real-time tracking in gastrointestinal system in vivo are still major challenges in basic research and clinical applications. Materials and methods: In this study, we fabricated a chitosan-coated alginate microcapsule loaded with in situ synthesized barium sulfate (CA/BaSO4 microcapsule) for oral Bifidobacterium delivery and real-time X-ray computed tomography (CT) imaging. CA/BaSO4 microcapsules containing the Bifidobacterium were prepared in situ by one-step electrostatic spraying method, and then coated with chitosan. Results: The results indicated that CA/BaSO4 microcapsules with an average diameter of approximately 200 mu m possessed favorable mechanical stability and X-ray attenuation capacity. Encapsulation of Bifidobacteria in the CA/BaSO4 microcapsules exhibited superior resistance to cryopreservation and gastric acid environment in vitro. After oral administration in mice, these CA/BaSO4 microcapsules could be real-time visualized by CT imaging and readily reached the intestine to release Bifidobacteria. Conclusion: The radiopaque CA/BaSO4 microcapsules provide a novel platform for efficient protection, non-invasive real-time monitoring and intestinal-targeted Bifidobacterium delivery.