Fluidic microgel assemblies with enhanced oral delivery of biologics alleviate colonic inflammation in murine and canine models

The efficacy of oral delivery of biologic drugs for inflammatory bowel disease (IBD) treatment is substantially compromised by the swift enzymatic degradation and insufficient retention of biologics in the gastrointestinal tract. Here, we report a simple method for fabricating fluidic microgel assemblies (FMGAs) by introducing the hydrogen bonds between the microgel surfaces. These FMGAs with water content of 77% are flowable yet immiscible with water. Upon oral administration, these FMGAs form a large-area physical adhesive coating on the intestinal surface, extending intestinal retention time to at least 48 hours. The intermicrogel spaces within the assemblies can efficiently harbor therapeutic biologics (such as exosomes and TNFα antibody), protect them from the harsh intestinal microenvironment, and enable efficient delivery to intestinal lesion sites to restore intestinal barrier function and microbiota diversity in mouse and beagle models of IBD. We believe that the fluidic microgel assembly strategy holds great promise for oral delivery of labile biologics for the treatment of diverse gastrointestinal diseases.