Arabinoxylans-Based Oral Insulin Delivery System Targeting the Colon: Simulation in a Human Intestinal Microbial...

Area of Science:

• Biomaterials Science
• Gastroenterology
• Pharmacology

Background:

• Insulin's therapeutic potential is limited by its oral instability and poor bioavailability.
• Developing effective oral delivery systems for biologics like insulin remains a significant challenge.

Purpose of the Study:

• To develop and evaluate arabinoxylans (AX) microcapsules as a carrier for colon-specific insulin delivery.
• To assess the stability, degradation, and microbial fermentation of AX microcapsules in a simulated human intestinal environment.
• To investigate the efficacy of insulin-loaded AX microcapsules in a diabetic rat model.

Main Methods:

• Arabinoxylans (AX) microcapsules loaded with insulin were prepared using enzymatic gelation and triaxial electrospray.
• In vitro evaluation of AX microcapsule behavior in a simulated human intestinal microbial ecosystem.
• In vivo assessment of oral insulin-loaded AX microcapsules in diabetic rats, monitoring serum glucose levels and insulin bioavailability.

Main Results:

• AX microcapsules demonstrated spherical morphology (average size 250 µm) and resisted upper gastrointestinal conditions.
• In vitro, AX microcapsules were primarily degraded in the ascending colon (70%), promoting beneficial short-chain fatty acid production.
• Significant increases in *Bifidobacterium* and *Lactobacillus* populations and a decrease in *Enterobacteriaceae* were observed.
• Oral administration of insulin-loaded AX microcapsules in diabetic rats reduced serum glucose by 75% and showed sustained effects for over 48 hours.
• Oral relative bioavailability of insulin was 13% and 8.7% for the tested doses.

Conclusions:

• AX microcapsules are a viable carrier for colon-specific insulin delivery, protected from degradation in the upper GI tract.
• The system is activated by gut microbiota, enhancing beneficial bacterial populations and SCFA production.
• Insulin-loaded AX microcapsules demonstrate significant hypoglycemic effects and improved oral bioavailability in diabetic rats, indicating potential for oral insulin therapy.