Development and evaluation of novel biodegradable chitosan based metformin intrapocket dental film for the management of periodontitis and alveolar bone loss in a rat model

Objective: The aim of this study was to develop a chitosan-metformin based intrapocket dental film (CMIDF) for applications in the treatment of periodontitis and alveolar bone loss in an rat model of periodontitis. Design: CMIDF inserts were fabricated by the solvent casting technique. The fabricated inserts were evaluated for physical characteristics such as folding endurance, surface pH, mucoadhesive strength, metformin content uniformity, and release. X-ray diffraction analysis indicates no crystallinity of metformin in presence of chitosan which confirmed successful entrapment of metformin into the CMIDF. Fourier-transform infrared spectroscopy revealed stability of CMIDF and compatibility between metformin and chitosan. Periodontitis was induced by a combination of Porphyromonas gingivalis-lipopolysaccharide injections in combinations with ligatures around the mandibular first molar. We divided rats into 5 groups (8 rats/group): healthy, untreated periodontitis; periodontitis plus CMIDF-A (1.99 +/- 0.09 mg metformin; total mass -4.01 +/- 0.05 mg), periodontitis plus CMIDF-B (2.07 +/- 0:06 mg metformin; total mass-7.56 +/- 0.09 mg), and periodontitis plus chitosan film (7.61 +/- 0.08 mg). After four weeks, mandibles were extracted to evaluate alveolar bone loss by micro-computerized tomography and histological techniques. Results: Alveolar bone was intact in the healthy group. Local administration of CMIDF resulted in significant improvements in the alveolar bone properties when compared to the untreated periodontitis group. The study reported here demonstrates that novel CMIDF showed good antibacterial activity and effectively reduced alveolar bone destruction in a rat model of experimental periodontitis. Conclusions: Novel CMIDF showed good antibacterial activity and improved alveolar bone properties in a rat model.