Decanoyl glycol chitosan: A novel pH-responsive thermogel for injectable drug delivery

This study introduces decanoyl glycol chitosan (DGC) as a novel pH-responsive injectable thermogel with enhanced dual sensitivity to temperature and pH, developed for controlled drug delivery applications. DGC was synthesized via N-decanoylation of glycol chitosan and exhibited unique multiphase sol-gel-sol transition behavior, in contrast to previous glycol chitosan-based thermogels that typically lack pH-responsiveness. The sol-gel transition occurred around 30-41 °C and reverted to a sol state at 50-53 °C, with transition temperatures tunable by pH, polymer concentration, and the degree of decanoylation. Notably, DGC is the first glycol chitosan-based thermogel that can significantly respond to both temperature and pH, offering a valuable advantage for biomedical use in pathological environments. Dynamic light scattering analysis confirmed the formation of self-assembled nanoparticles in aqueous media, with pH- and temperature-dependent size distribution. Doxorubicin (DOX) was effectively encapsulated into the DGC matrix, and the resulting thermogel demonstrated a sustained, pH-dependent drug release, reaching approximately 94 % cumulative release under acidic conditions (pH 5.0) over 6 days. In vivo studies confirmed effective subcutaneous gel formation with excellent biocompatibility and minimal inflammatory response or cytotoxicity. These results highlight DGC thermogel as a smart, multifunctional biomaterial with customizable properties and favorable safety, making it highly suitable for injectable drug delivery systems.