Abstract

Oral therapy for inflammatory bowel disease (IBD) is hindered by poor colonic targeting and drug burst release from carriers within the upper gastrointestinal tract. To address these drawbacks, we engineered the bigel microspheres (NPs@Alg/AO-Ca) using electrospraying technology for colon-targeted delivery of supramolecular self-assembled nanoparticles (BE-NPs) composed of berberine (BBR) and epigallocatechin gallate (EGCG). The platform forms multiphase bigel microspheres, in which AO-based oleogel-rich domains are dispersed within a calcium-crosslinked alginate network. This multiphase matrix facilitates the colon delivery. In vitro and in vivo results demonstrated that NPs@Alg/AO-Ca responded to the colonic milieu to release BE-NPs, thereby leveraging the synergy between BBR and EGCG. Consequently, the system exhibits pronounced anti-inflammatory efficacy and barrier-restorative capacity in the murine IBD models, offering a potential therapeutic strategy.