Nanomedicine for treating inflammatory bowel disease
(Nanowerk News) Chronic inflammatory bowel diseases (IBD), such as Crohn’s disease and ulcerative colitis, are on the rise worldwide. The benefits of current treatment are limited by problematic side effects.
In the journal Applied chemistry (“Anti-inflammatory Glycocalyx Mimicking Nanoparticles for the Treatment of Colitis: Construction and In Vivo Evaluation”), a South Korean research team has now introduced a new treatment method. It is based on nanoparticles that mimic a special carbohydrate coating (glycocalyx) located on inflamed intestinal cells, and which trigger an anti-inflammatory effect in diseased parts of the intestine.
Abdominal cramps and severe diarrhea, often accompanied by significant weight loss, are some of the symptoms that patients with IBD suffer repeatedly, often for weeks on end. The cause of this condition is still unclear but seems to involve a malfunction of the immune system. The cure is yet to be seen. Current treatment aims to reduce symptoms with anti-inflammatory drugs, such as 5-aminosalicylic acid (5-ASA), corticosteroids, and immunomodulators.
Their long-term use is not recommended because of their severe side effects, such as the high risk of infection due to immunosuppression. A team led by Hee-Seung Lee and Sangyong Jon at the Korea Advanced Institute of Science and Technology (KAIST) have now developed an innovative approach to medication that can be taken orally and targets inflamed sites in the digestive tract, minimizing systemic effects. .
The starting point for their approach is the glycocalyx, the carbohydrate-rich layer that lines cells on the surface of the gut. Beneficial gut bacteria, which have a suitable glycocalyx, attach to this layer. With diseases of the IBD family, the carbohydrate pattern of the glycocalyx in inflamed areas of the intestine is so altered that pathogenic bacteria can attach to and enter the mucous membranes.
The team developed nanoparticles that mimic the pattern of the glycocalyx. Starting with the five most common sugar monomers found in nature, they produce a collection (“library of matter”) of various polymer chains having one, two, three, four, or five of these sugars in random order and composition as side chains. These polymer chains assemble into nanoparticles. They also attach bilirubin molecules. Bilirubin is a bile pigment which is an antioxidant naturally produced by the body and has anti-inflammatory effects.
When administered orally to mice with IBD, some versions of these nanoparticles reduced symptoms significantly better than 5-ASA drugs. Nanoparticles with mannose and N-acetylglucosamine were the most effective. These two sugars increase the uptake of nanoparticles by active macrophages in the inflamed gut, and bilirubin very efficiently inhibits the inflammatory activity of these immune cells. Concentrations of certain inflammatory cytokines are significantly reduced, production of anti-inflammatory factors is stimulated, and oxidative stress is reduced. Immunosuppressive effect is limited to inflamed intestinal areas, minimizing unfavorable systemic side effects.
