Construction and functional evaluation of oral long-acting insulin hydrogel microparticles based on physical and chemical double crosslinking

The objective of this study was to enhance the convenience and effectiveness of diabetes treatment by developing hydrogel microparticles as an oral insulin delivery system, aiming to reduce the necessity for frequent treatments. The hydrogel microparticles were prepared with polysaccharides through a combination of physical and chemical crosslinking method, they achieved good results in insulin loading efficiency (70 %), insulin release efficiency (98 %) and sustained release time (>20 h). The effective transmembrane transport was validated using an intestinal epithelial cell model, which demonstrated a continuous hypoglycemic effect lasting from 6 to 26 h in a type 2 diabetes mouse model. Additionally, the relative bioavailability of insulin reached 30.14 ± 2.62 %, representing a significant breakthrough in the field of oral insulin delivery carriers. Furthermore, oral insulin hydrogel exhibited a substantial improvement in insulin resistance, organ damage, and diabetes-related complications stemming from hyperglycemia. These compelling findings underscore the potential of hydrogel microparticles as a cost-effective and valuable strategy for oral drug delivery in diabetes treatment.