Sustained Release Strategy Designed for Lixisenatide Delivery to Synchronously Treat Diabetes and Associated Complications

Diabetes and its complications have become a global challenge of public health. Herein, we aimed to develop a long-acting delivery system of lixisenatide (Lixi), a glucose-dependent antidiabetic peptide, based on an injectable hydrogel for the synchronous treatment of type 2 diabetes mellitus (T2DM) and associated complications. Two triblock copolymers, poly(e-caprolactone-co-glycolic acid)–poly(ethylene glycol)–poly(e-caprolactone-co-glycolic acid) and poly(d,l-lactic acid-co-glycolic acid)–poly(ethylene glycol)–poly(d,l-lactic acid-co-glycolic acid) possessing temperature-induced sol–gel transitions, were synthesized by us. Compared to the two single-component hydrogels, their 1/1 mixture hydrogel not only maintained the temperature-induced gelation but also exhibited a steadier degradation profile in vivo. Both in vitro and in vivo release studies demonstrated that the mixture hydrogel provided the sustained release of Lixi for up to 9 days, which was attributed to balanced electrostatic interactions b...