Introduction

On June 26, 2025, the team of Harry Brumer and Laura M. Sly from the University of British Columbia published an article titled "Bespoke plant glycoconjugates for gut microbiota-mediated drug targeting" in Science. The team has developed a new drug design method that can deliver drugs directly to specific parts of the gastrointestinal tract (GI). This Drug Delivery System, called "GlycoCaging", is based on a customized glycan complex of complex plant oligosaccharides. A proof-of-concept study on mice showed that the system can specifically release drugs to the lower intestine at a dose 10 times lower than the current dose of inflammatory bowel disease treatment drugs.

Article Overview

The "GlycoCaging" technology developed by the team of the University of British Columbia in Canada is based on the covalent binding of Plant Oligosaccharides to drugs, and uses the specific enzymatic properties of intestinal flora to achieve precise gastrointestinal drug delivery. In the inflammatory bowel disease (IBD) mouse model, the system reduced the dose of dexamethasone to 1/10 of the traditional therapy, but achieved the same anti-inflammatory effect, while reducing the serum drug concentration by 19.8 times, significantly reducing systemic toxicity. Analysis of the microbiota of 33 IBD patients showed that all subjects had the enzyme activity to metabolize the GlycoCaging, confirming its clinical applicability. This technology provides an innovative path to solve the problem of targeted delivery of oral drugs, and is expected to expand to the reuse of various drugs such as Antibacterial Drugs and immunosuppressants.

Main Content

Technical Background: Dilemma of Inflammatory Bowel Disease Treatment

IBD includes Crohn's disease and ulcerative colitis, and the global incidence continues to rise. Canada is a country with a high incidence of IBD. As of 2023, there are about 322,600 patients, and the age of onset is concentrated between 19 and 29 years old. At present, mainstream treatments such as anti-inflammatory steroids need to be taken orally or intravenously, but these drugs have significant defects.

Systemic Toxicity

It is easy to cause side effects such as osteoporosis, hypertension, and diabetes.

Poor Targeting

The drug is absorbed in large quantities in the upper gastrointestinal tract, and the dose reaching the intestinal lesions is insufficient, forcing doctors to use high-dose treatment.

Therefore, achieving precise drug delivery in specific parts of the gastrointestinal tract has become a difficult problem that the medical community has long explored.

The Core Principle of GlycoCaging

Inspired by dietary fiber metabolism, the research team developed a targeted delivery system based on plant oligosaccharides.

Design Inspiration

Certain fiber molecules in fruits and vegetables (such as Xyloglucan) can only be broken down by enzymes (such as Xyloglucanase) secreted by intestinal bacteria.

Mechanism of Action

• Drugs (such as steroids) are combined with customized plant oligosaccharides through glycosidic bonds to form a "GlycoCaging-drug" complex.
• The hydrophilic oligosaccharide shell prevents drug absorption in the upper digestive tract until it reaches the lower intestine.
• Intestinal flora-specific enzymes catalyze the decomposition of oligosaccharides and release drugs to the site of inflammation.

Technical Advantages

Using the natural metabolic pathways of the human intestinal flora to achieve precise release in the "biological key unlocking" style.

Fig. 1 Targeted drug delivery using the xyloglucan utilization system of human intestinal Bacteroides. (Ma, et al., 2025)

Animal Experiment Verification: 10-fold Reduction In Dose, Significantly Reduced Side Effects

The team conducted experiments for up to 9 weeks in two IBD Mouse Models.

Model 1 (T Cell Transfer Colitis)

• Glycocaged dexamethasone (XXXG-Dex) uses only 1/3 to 1/10 of the conventional dose, and the anti-inflammatory effect is equivalent or even better.
• The drug concentration in serum and tissues is significantly reduced, proving that upper gastrointestinal absorption is inhibited.

Model 2

• GlycoCagingtechnology completely eliminates the "off-target effect" of drugs on non-intestinal tissues.
• In animal experiments, only intestinal inflammation is relieved, and other parts of the body are not affected by drugs.

In Vitro Verification

Enzymatic release experiments show that GlycoCaging complexes can be specifically hydrolyzed in a simulated intestinal environment, verifying the feasibility of in vivo release.

Clinical transformation potential: adaptable to a variety of drugs and patient groups

Drug Reuse Value

• It can be used for powerful drugs such as dexamethasone that are limited by side effects, and expand the treatment window through targeted delivery.
• The scope of application is extended to antibacterial compounds, other anti-inflammatory drugs, etc., covering a variety of diseases such as intestinal infections and IBD.

Patient Applicability

• Analysis of fecal samples of 33 IBD patients (including remission and active phases) showed that the intestinal flora of all subjects can activate sugar cage drugs.
• The global gene marker database verifies that most people have the genetic basis for metabolizing this oligosaccharide.

Research Outlook: A Leap from "Symptomatic Treatment" to "Precise Targeting"

This technology uses natural dietary fiber components as carriers, combining biocompatibility and targeting specificity. The paper published by the research team pointed out that GlycoCaging is expected to:

• Save candidate drugs that have been shelved due to systemic toxicity.
• Reduce the dose of existing gastrointestinal drugs and improve the quality of life of patients.
• Provide a universal platform for targeted delivery of oral drugs and promote innovation in the treatment of digestive system diseases.

Currently, the team is promoting the verification of this technology in more drug types and exploring its application path in human clinical trials.

Summary

GlycoCaging technology simulates the intestinal flora metabolic pathway of dietary fiber to construct a "bio-key triggered" drug release system, realizing the "dose-toxicity-efficacy" triangle optimization of gastrointestinal drug delivery for the first time. Its core innovation lies in the use of the biocompatibility and flora specificity of natural oligosaccharides, which not only circumvents the immunogenicity problem of traditional carriers, but also breaks through the targeting limitations of pH-sensitive materials. Studies have confirmed that this technology can save candidate drugs that have been shelved due to systemic toxicity, and provide low-toxic and efficient treatment options for diseases such as inflammatory bowel disease and intestinal infections. With the advancement of Phase I clinical trials in 2026, this "bacteria-based" delivery strategy may reshape the drug development paradigm for digestive system diseases.

Related Services & Products

• Plant-derived Carbohydrate-based Glycomedicine Development
• Oligosaccharides-based Glycomedicine Development
• Plant Polysaccharides Separation
• Plant Polysaccharides Structure Analysis
• Cellulose/ Hemicellulose/ Lignin Content Analysis
• Glycobiology Disease Model Construction Service
• CRISPR-Pro-based Services
• Mice or Rat Transgenic Services
• In Vivo Glycobiology Disease Model Screening Service
• Intestinal Cells-based In Vitro Screening Service
• Monosaccharide
• Disaccharide
• Oligosaccharide
• Polysaccharide

Reference

1. Ma, W. J., et al. (2025). Bespoke plant glycoconjugates for gut microbiota–mediated drug targeting. Science, 388(6754), 1410-1416. DOI: 1126/science.adk7633.