Injectable Temperature/Glucose Dual-Responsive Hydrogels for Controlled Release of Insulin

Self-regulating insulin controlled-release systems have gained more attention due to their advantages of timely response to blood glucose change and avoiding side effects caused by the high-frequency injection. In this paper, the temperature-responsive monomer N-isopropylacrylamide (NIPAM) and glucose-responsive monomer 3-acrylamidophenylboronic acid (AAPBA) are copolymerized and then grafted with alginate to prepare temperature/glucose dual-responsive copolymers alginate-g-P(NIPAM-co-AAPBA) (Alg-g-PNA). The temperature and glucose responsiveness under different conditions, rheological characteristics, glucose-mediated insulin release, and biotoxicity of the Alg-g-PNA copolymers are studied. The results show that the copolymer solution is in the sol state at 10 °C and insulin can be dispersed uniformly, while it turns into the gel state when the temperature rises to physiological 37 °C for in situ delivery of insulin. Due to the sensitivity to blood glucose levels, the hydrogels can quickly respond to the increase in blood glucose and undergo the gel-to-sol transition and release insulin to reduce blood glucose when the environmental blood glucose rises. Moreover, the hydrogels have good sol–gel transition reversibility in response to changes between normoglycemic and hyperglycemic levels. The cell cytotoxicity results show that the hydrogels have good biocompatibility to be a safe carrier for insulin delivery. The proposed injectable temperature/glucose dual-responsive hydrogels in this study provide a novel type of self-regulating insulin delivery systems for diabetes therapy.