Anti‐inflammatory Glycocalyx‐Mimicking Nanoparticles for Colitis Treatment: Construction and In Vivo Evaluation

Common medications for treating inflammatory bowel disease (IBD) have limited therapeutic efficacy and severe adverse effects. This underscores the urgent need for novel therapeutic approaches that can effectively target inflamed sites in the gastrointestinal tract upon oral administration, exerting potent therapeutic efficacy while minimizing systemic effects. Here, we report the construction and in vivo therapeutic evaluation of a library of anti‐inflammatory glycocalyx‐mimicking nanoparticles (designated GlyNPs) in a mouse model of IBD. The anti‐inflammatory GlyNP library was created by attaching bilirubin (BR) to a library of glycopolymers composed of random combinations of the five most naturally abundant sugars. Direct in vivo screening of 31 BR‐attached anti‐inflammatory GlyNPs via oral administration into mice with acute colitis led to identification of a candidate GlyNP capable of targeting macrophages in the inflamed colon and effectively alleviating colitis symptoms. These findings suggest that the BR‐attached GlyNP library can be used as a platform to identify anti‐inflammatory nanomedicines for various inflammatory diseases. A library of bilirubin‐attached glycocalyx‐mimicking nanoparticles was constructed as a platform enabling identification of an anti‐inflammatory nanomedicine. Direct in vivo screening of the nanoparticle library by oral administration into mice with acute colitis led to identification of a candidate anti‐inflammatory nanomedicine capable of targeting macrophages in the inflamed colon and effectively alleviating colitis symptoms.