Nanotechnology

Utilizing Nanomedicine to Overcome Inflammatory Bowel Disease

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The prevalence of chronic inflammatory bowel disease (IBD), including Crohn’s disease and ulcerative colitis, is increasing globally. The problematic side effects of modern medicines limit their beneficial effects. A team of South Korean researchers just published a new treatment approach in the journal Applied chemistry.

Utilizing Nanomedicine to Overcome Inflammatory Bowel Disease

Image Credit: Applied Chemistry

It is based on nanoparticles that mimic a unique layer of carbohydrates called the glycocalyx, which is found in inflamed intestinal cells and causes an anti-inflammatory effect on diseased areas of the intestine.

Patients with IBD often experience these symptoms, sometimes for weeks, including abdominal cramps, severe diarrhea and significant weight loss. Although the exact cause of this medical condition is unknown, a compromised immune system appears to be a contributing factor. There is still no cure in sight.

Anti-inflammatory drugs such as 5-aminosalicylic acid (5-ASA), corticosteroids, and immunomodulators are currently used as treatment to reduce symptoms. Because of its significant side effects, such as an increased risk of infection caused by immunosuppression, long-term use is not recommended.

A group at the Korea Advanced Institute of Science and Technology (KAIST) led by Hee-Seung Lee and Sangyong Jon have now created a new strategy for drugs that can be administered orally that target areas of inflammation in the digestive tract while limiting systemic effects. .

The glycocalyx, the carbohydrate-rich layer that covers cells on the surface of the gut, serves as the basis for their strategy. Beneficial gut bacteria attach to this covering using the appropriate glycocalyx.

The pattern of carbohydrate glycocalyx in inflamed areas of the intestine is so altered in diseases of the IBD family that pathogenic bacteria can attach to and infiltrate the mucous membranes.

The group created nanoparticles that resemble the structure of the glycocalyx. They created a collection of various polymer chains called a “library of substances” using the five sugar monomers most commonly found in nature as a starting point. These side chains contain one, two, three, four, or five of these sugars in random order and composition.

These polymer chains come together to form nanoparticles. In addition, the bilirubin molecule combines. A bile pigment called bilirubin, which the body produces naturally as an antioxidant and has anti-inflammatory properties.

Several variations of these nanoparticles greatly reduced symptoms when administered orally to mice with IBD compared to 5-ASA drugs. The most efficient nanoparticles are those containing mannose and N-acetylglucosamine.

With the help of these two sugars, the active macrophages in the inflamed intestine are better able to absorb the nanoparticles, and the bilirubin effectively reduces their inflammatory activity.

Certain inflammatory cytokines are significantly decreased, production of anti-inflammatory factors is enhanced, and oxidative stress is minimized. The immunosuppressive impact is limited to the inflammatory bowel portion, reducing the possibility of negative systemic side effects.

Journal Reference

Yoo, D., et al. (2023) Anti-inflammatory Glycocalyx Mimicking Nanoparticles for the Treatment of Colitis: Construction and In Vivo Evaluation. Applied chemistry. doi:10.1002/anie.202304815.

Source: https://onlinelibrary.wiley.com/

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