Capsulated Cellular Nanosponges for the Treatment of Experimental Inflammatory Bowel Disease.

Abstract

Inflammatory bowel disease (IBD) is a chronic gastrointestinal tract disorder characterized by uncontrolled inflammatory responses to the disrupted intestinal epithelial barrier and gut microbiome dysbiosis. Currently available small-molecule immunosuppressive agents and anticytokine biologics show limited potency, mainly due to the complexity of the inflammatory network involved in IBD. Here, we develop an oral formulation of macrophage membrane-coated nanoparticles capsulated in enteric polymer-coated gelatin capsules (denoted "cp-MΦ-NPs") for IBD treatment. The capsules protect the nanoparticles from gastric degradation and allow for targeted delivery to the colon. At the inflamed colon, cp-MΦ-NPs act as macrophage decoys that bind and neutralize pro-inflammatory cytokines. The in vivo treatment efficacy of cp-MΦ-NPs is tested in a mouse model of dextran sulfate sodium-induced colitis. In both prophylactic and delayed treatment regimens, the oral delivery of cp-MΦ-NPs significantly alleviates IBD severity, reflected by reduced intestinal inflammation and intestinal barrier restoration. Overall, cp-MΦ-NPs provide a biomimetic nanomedicine strategy for the treatment of IBD.