Grant: Cat Gr: Develop./validation of new biomedical techniques/technolo.- General Pool

The incidence of Inflammatory Bowel Diseases (IBD, comprising Crohn's disease and ulcerative colitis) is rising globally and there is an especially high prevalence among Canadians (ca. 1 in 140 individuals). IBD currently has no cure, and the efficacy and safety of many IBD drugs used to alleviate symptoms is limited by absorption in the stomach and small intestine, which causes these drugs to circulate throughout the body, leading to side-effects. In this project, we will use our specialist knowledge of dietary fibre metabolism by the human gut microbiota (HGM) to develop a new route to deliver drugs directly to the lower gastrointestinal tract and improve the treatment of IBD. By connecting key IBD drugs to a large, hydrophilic vegetable carbohydrate through a specific chemical bond - a technique we call "GlycoCaging" - general absorption in the GI tract will be prevented. However, once this conjugate reaches the lower GI tract, where our HGM resides, bacterial glycosidases will cleave the chemical bond, releasing the cargo as the free drug. This microbiota-mediated release will maximize the local dose and efficacy of the drug while minimizing systemic uptake and side-effects. The GlycoCaged versions of IBD drugs to be developed in this project may lead to a new treatment paradigm and represent a made-in-Canada solution to alleviate the suffering of individuals with IBD and other GI diseases.