Preparation Of Berberine-Loaded Thermo-Sensitive Hydrogels And Evaluation Of Its Antibacterial Effect On Bacteria

[Objective] This study aimed to fabricate the berberine(BBR)-loaded chitosan/sodium β-glycerophosphate(CS/β-GP)thermosensitive hydrogels and assess its potential role in the treatment of chronic periodontitis by characterizing its physicochemical properties,biocompatibility and in vitro antibacterial effects.[Methods] CS/β-GP thermosensitive hydrogel was prepared by physical cross-linking method,and BBR was added to the CS/β-GP temperature-sensitive hydrogel by embedding method.According to the different drug loading,25μg·m L-1BBR/CS/β-GP,50μg·m L-1BBR/CS/β-GP,100μg·m L-1BBR/CS/β-GP thermosensitive hydrogel was prepared.The p H and gelation time at 37℃ of each group were recorded.Micromorphology,rheological properties,and in vitro drug release rates were detected.The Cell counting kit-8 method was used to detect the effects of hydrogels on the proliferation of periodontal ligament cells and to assess cell compatibility.The inhibition zone experiment was used to analyze each group’s in vitro antibacterial effect on periodontal pathogens Porphyromonas gingivalis(P.gingivalis)ATTCC33277and Fusobacterium nucleatum(F.nucleatum)ATCC25586.[Results] The gels in each group have good injectability at 4 ℃,and the phase transition can be completed around body temperature.The phase transition temperature of CS/β-GP is 37.26 ℃,and the hydrogels of each group can smoothly complete the gelation transformation within 3 minutes at 37℃.The p H of gel is between 6.5 ~ 7.4,which is in line with the physiological range of human.The results of gel electron microscopy presented a three-dimensional network structure interconnected.BBR/CS/β-GP hydrogels can continuously release BBR in vitro,and the cumulative release rate can reach 70%-80% in 24 hours.No obvious cell toxicity was seen in the co-cultivation of gels and periodontal ligament cells for 1,3,5 days in each group.Each group of hydrogels can inhibit the growth of periodontal pathogens P.gingivalis ATTCC33277 and F.nucleatum ATCC25586,and there was a significant difference in the bacteriostatic results between the 100μg·m L-1BBR/CS/β-GP group and the CS/β-GP group(P<0.05).[Conclusion] 100μg·m L-1BBR/CS/β-GP thermosensitive hydrogel has stable physical and chemical properties,good biocompatibility,and has a clear bacteriostatic effect on periodontal pathogens.It can be used as a local treatment candidate for chronic periodontitis.