The objective of the present study was to develop a pH-sensitive drug delivery system by using polymethylmethacrylate-grafted gellan gum (PMMA-g-GG). PMMA-g-GG was synthesized by free radical polymerization reaction by using redox initiator ceric ammonium nitrate (CAN), and a series of graft copolymers were prepared with varying concentrations of methylmethacrylate (MMA) and CAN. Grafting parameters such as the percentage and efficiency of grafting were calculated, and the effect of monomer as well as initiator concentration was studied on the grafting yield. Optimization was done by one optimal response surface methodology. The batch with a better percentage grafting and grafting efficiency was selected and characterized by elemental analysis (CHN), FT-IR, DSC, PXRD, 1H-NMR, and SEM. Furthermore, acute oral toxicity study and histopathological analysis suggested non-toxic and biocompatible nature of the grafted gum. Metformin hydrochloride pellets were prepared using PMMA-g-GG, characterized in detail, and assessed for biocompatibility and efficacy. PMMA-g-GG-based formulation (M4) exhibited a pH-sensitive as well as sustained release of the drug over the period of 12 h and the release profile followed Peppas model. In vivo efficacy studies indicated a promising antidiabetic potential of the prepared formulation. Thus, PMMA-g-GG-based formulations can be implicated as novel drug delivery systems for facilitated antidiabetic therapy in the near future. Graphical abstract.
Keywords: Antidiabetic therapy; Free radical polymerization; Gellan gum; Grafting; Metformin hydrochloride; pH-sensitive drug delivery.