A team of researchers from the Korea Advanced Institute of Science and Technology has developed a new treatment for chronic inflammatory bowel disease (IBD). based on nanoparticles that mimic a special layer of carbohydrates (glycocalix) found in inflamed intestinal cells and cause an anti-inflammatory effect in diseased areas of the intestine.
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Chronic inflammatory bowel diseases (IBD), such as Crohn’s disease and ulcerative colitis, are on the rise worldwide. The benefits of modern drugs are limited by their unpleasant side effects.
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Stomach cramps and severe diarrhea, often accompanied by significant weight loss, are some of the symptoms that IBD patients experience repeatedly, often for weeks on end.
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The causes of this disease remain unclear, but appear to be related to malfunctions in the immune system. There is no cure yet.
Current therapies attempt to reduce symptoms with anti-inflammatory drugs such as 5-aminosalicylic acid (5-ASA), corticosteroids, and immunomodulators. Its long-term use is not recommended due to its serious side effects such as a high risk of infection due to immunosuppression.
This new study, published in the scientific journal Angewandte Chemie, has developed an innovative treatment that it can be taken orally and acts on inflamed areas of the gastrointestinal tract, minimizing systemic effects.
The starting point was the glycocalyx, the carbohydrate-rich layer that lines the cells on the surface of the intestine. Beneficial intestinal bacteria, which have their own glycocalyx, are attached to this layer.
In familial diseases of IBD, the carbohydrate composition of the glycocalyx of the inflamed intestines changes to such an extent that pathogenic bacteria can attach to the mucous membrane and penetrate into it.
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The team developed nanoparticles that mimic the structure of the glycocalyx. Starting with five of nature’s most common sugar monomers, they created a collection (“substance library”) of various polymer chains that have one, two, three, four, or five of these sugars in random order and composition as side chains.
These polymer chains combine to form nanoparticles. They also added bilirubin molecules. Bilirubin is a bile pigment that is an antioxidant naturally produced by the body with anti-inflammatory effects.
When administered orally to mice with IBD, some versions of these nanoparticles reduced symptoms significantly better than 5-ASA.
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The most effective were nanoparticles with mannose and N-acetylglucosamine. These two sugars increase uptake of the nanoparticles by activated macrophages in the inflamed gut, and bilirubin is very effective at inhibiting the inflammatory activity of these immune cells.
The concentration of some inflammatory cytokines is significantly reduced, the production of anti-inflammatory factors is stimulated and oxidative stress is reduced. The immunosuppressive effect is limited to inflamed areas of the intestine, which minimizes adverse systemic side effects.
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