Arabinoxylans-Based Oral Insulin Delivery System Targeting the Colon: Simulation in a Human Intestinal Microbial Ecosystem and Evaluation in Diabetic Rats

Arabinoxylans (AX) microcapsules loaded with insulin were prepared by enzymatic gelation of AX, using a triaxial electrospray method. The microcapsules presented a spherical shape, with an average size of 250 mu m. The behavior of AX microcapsules was evaluated using a simulator of the human intestinal microbial ecosystem. AX microcapsules were mainly (70%) degraded in the ascending colon. The fermentation was completed in the descending colon, increasing the production of acetic, propionic, and butyric acids. In the three regions of the colon, the fermentation of AX microcapsules significantly increased populations of Bifidobacterium and Lactobacillus and decreased the population of Enterobacteriaceae. In addition, the results found in this in vitro model showed that the AX microcapsules could resist the simulated conditions of the upper gastrointestinal system and be a carrier for insulin delivery to the colon. The pharmacological activity of insulin-loaded AX microcapsules was evaluated after oral delivery in diabetic rats. AX microcapsules lowered the serum glucose levels in diabetic rats by 75%, with insulin doses of 25 and 50 IU/kg. The hypoglycemic effect and the insulin levels remained for more than 48 h. Oral relative bioavailability was 13 and 8.7% for the 25 and 50 IU/kg doses, respectively. These results indicate that AX microcapsules are a promising microbiota-activated system for oral insulin delivery in the colon.

Automated summary

Arabinoxylans (AX) microcapsules loaded with insulin were prepared and evaluated using a simulator of the human intestinal microbial ecosystem. The microcapsules mainly degraded in the ascending colon and increased populations of beneficial bacteria while decreasing harmful bacteria. Oral delivery of the AX microcapsules in diabetic rats showed hypoglycemic effects and sustained insulin levels, indicating their potential as an oral insulin delivery system.