Plant fibers may help IBD drugs reach the lower gut

A new drug delivery method could improve treatments for inflammatory bowel disease (IBD) like ulcerative colitis and Crohn’s disease.

Currently available oral drugs for IBD must transit the entire upper digestive tract before they get to the lower gastrointestinal (GI) tract—the area where they’re actually needed, says Laura Sly, a professor in the pediatrics department at the University of British Columbia (UBC). This results in the drugs being absorbed too early, which causes side effects and dilutes their effectiveness in the lower GI tract. “They have to enter circulation and go into their bloodstream, and we still have a hard time getting sufficient amounts of drug to the affected area for patients.”

Sly, chemistry professor Harry Brumer, and a group of other researchers at the UBC developed GlycoCage, a delivery technology designed to protect IBD drugs from the rest of the digestive system until they reach the lower GI tract. In vivo data for this approach were released in Science on May 1 (DOI: 10.1126/science.adk7633).

GlycoCaging attaches a plant-based oligosaccharide—similar to one found in the fiber that’s part of human diets—to the IBD drug. These oligosaccharides are broken down only by bacteria present in the lower GI tract. Attaching the oligosaccharide to the drug allows the latter to move through the digestive tract and reach the large intestine before it’s broken down.

In two mouse models of intestinal inflammation and colitis, the steroid dexamethasone with a GlycoCage was mostly absorbed in the lower GI tract; when the mice were given traditional dexamethasone, it was detected in blood serum and tissue. Although GlycoCaged dexamethasone was given at a lower dose, it was similar to or better than noncaged dexamethasone in reducing inflammation.

This research builds on previous work investigating the gut microbiome, Brumer says.

“It was that basic fundamental research that we did, just exploring how our gut bacteria work. That gave us the insight and the inspiration to try to turn this into something to help people.”