Selenium nanoparticles as versatile carriers for oral delivery of insulin: Insight into the synergic antidiabetic effect and mechanism

Abstract Oral insulin delivery has been plagued by limited bioavailability. This work reports selenium nanoparticles (SeNPs) for oral insulin delivery to overcome the absorption barrier. Insulin-loaded SeNPs (INS-SeNPs) were fabricated by ionic cross-linking/ in situ reduction and characterized by particle size and drug entrapment. The resultant INS-SeNPs were 120 nm around in particle size with high drug loading. INS-SeNPs exhibited controllable insulin release and outstanding stability in the digestive fluids. INS-SeNPs caused a significant hypoglycemic effect in both normal and diabetic rats. The pharmacological bioavailability was up to 9.15% relative to subcutaneous insulin. Likewise, the blood insulin evidently increased in terms of INS-SeNPs. Ex vivo intestinal imaging and cell experiments showed the excellent performance of INS-SeNPs in intestinal permeability. INS-SeNPs could alleviate oxidative stress, improve pancreatic islet function, and promote glucose utilization. Our study provides proof of concept for using SeNPs to orally deliver insulin, jointly potentiating the antidiabetic effect.