Intestinal-Target\nand Glucose-Responsive Smart Hydrogel\ntoward Oral Delivery System of Drug with Improved Insulin Utilization

An intelligent insulin delivery system targeting intestinal\nabsorption\nand glucose responsiveness can enhance the bioavailability through\noral insulin therapy, offering promising diabetes treatment. In this\npaper, a glucose and pH dual-response polymer hydrogel using carboxymethyl\nagarose modified with 3-amino-phenylboronic acid and l-valine\n(CPL) was developed as an insulin delivery carrier, exhibiting excellent\nbiocompatibility and effective insulin encapsulation. The insulin\nencapsulated in the hydrogel (Ins-CPL) was released in a controlled\nmanner in response to the <i>in vivo</i> stimulation of\nblood glucose and pH levels with higher levels of intracellular uptake\nand utilization of insulin in the intestinal environment simultaneously.\nNotably, the Ins-CPL hydrogel effectively regulated blood sugar in\ndiabetic rats over a long period by simulating endogenous insulin,\nresponding to changes in plasma pH and glucose levels, and overcoming\nthe intestinal epithelium barrier. This indicates a significant boost\nin oral insulin bioavailability and broadens its application prospects.