The prevalence of chronic inflammatory bowel disease (IBD), including Crohn’s disease and ulcerative colitis, is rising globally. The problematic side effects of modern drugs restrict their beneficial effects. A South Korean research team has just published a novel treatment approach in the journal Angewandte Chemie.
It is based on nanoparticles that imitate a unique coating of carbohydrates called the glycocalyx, which is found on inflamed bowel cells and causes anti-inflammatory effects in the diseased areas of the intestine.
Patients with IBD frequently experience these symptoms, sometimes for weeks at a time, including stomach cramps, severe diarrhea, and significant weight loss. Though this medical condition's exact cause is unknown, a compromised immune system appears to be a contributing factor. There is still no remedy in sight.
Anti-inflammatory drugs such as 5-aminosalicylic acid (5-ASA), corticosteroids, and immunomodulators are currently used as a treatment to lessen symptoms. Due to its significant adverse effects, such as an elevated risk of infection caused by immunosuppression, their prolonged usage is not advised.
A group at the Korea Advanced Institute of Science and Technology (KAIST) led by Hee-Seung Lee and Sangyong Jon has now created a novel strategy for a drug that could be administered orally that targets the inflammatory regions in the gastrointestinal tract while limiting systemic effects.
The glycocalyx, a layer rich in carbohydrates that covers the cells on the surface of the intestine, served as the foundation for their strategy. Beneficial gut bacteria adhere to this covering using their own corresponding glycocalyx.
The glycocalyx carbohydrate patterns of inflamed intestinal areas are so changed in diseases of the IBD family that pathogenic bacteria can cling and infiltrate the mucous membrane.
The group created nanoparticles that resemble the glycocalyx structure. They created a collection of various polymer chains called a “substance library” using the five sugar monomers that are most frequently found in nature as a starting point. These side chains contain one, two, three, four, or five of these sugars in a random sequence and composition.
These polymer chains aggregate to form nanoparticles. Additionally, bilirubin molecules were joined. A bile pigment called bilirubin, which the body naturally produces as an antioxidant and has anti-inflammatory properties.
Some variations of these nanoparticles considerably lessened symptoms when given orally to mice with IBD compared to the drug 5-ASA. The most efficient nanoparticles were those that included mannose and N-acetylglucosamine.
With the help of these two sugars, active macrophages in the inflamed intestine are better able to absorb nanoparticles, and bilirubin effectively reduces their inflammatory activity.
Certain inflammatory cytokines are significantly decreased, anti-inflammatory factor production is promoted, and oxidative stress is minimized. The immunosuppressive impact is restricted to the inflammatory sections of the gut, reducing the likelihood of negative systemic side effects.
Yoo, D., et al. (2023) Anti-inflammatory Glycocalyx-Mimicking Nanoparticles for Colitis Treatment: Construction and In Vivo Evaluation. Angewandte Chemie. doi:10.1002/anie.202304815.