Design, preparation, and characterization of injectable thermosensitive polymer-based hydrogels with enhanced mechanical properties for sustained liraglutide release

With increasing prevalence and incidence of type 2 diabetes and obesity, liraglutide, a glucagon-like peptide (GLP)-1 agonist, has drawn much attention for its favorable effects. However, the fact that it requires daily subcutaneous administration results in low patient compliance. Herein, we aimed to develop injectable and thermosensitive Pluronic F127-based and chitosan-based hydrogels incorporating hyaluronic acid, Capryol 90, and β-glycerophosphate (β-GP) for long-term glycemic control. Incorporating hyaluronic acid, Capryol 90, and β-GP significantly influenced the rheological properties and morphologies of the hydrogels. In addition, both Pluronic-based and chitosan-based hydrogels exhibited excellent biocompatibility and acceptable injection forces. Pluronic-based hydrogels showed a mild burst release compared to chitosan-based hydrogels, which was attributed to their rheological properties, morphology, and molecular interactions between liraglutide and the hydrogel materials. Following a single subcutaneous administration in rats, Pluronic-based hydrogels exhibited favorable pharmacokinetics as well as a low initial burst release and prolonged drug exposure for 72 h, which was superior to chitosan-based hydrogels. In conclusion, injectable, thermosensitive Pluronic-based hydrogels incorporating hyaluronic acid and Capryol 90 demonstrated promising properties as controlled delivery systems for the weekly administration of liraglutide.