Study Of Hydrogel For Photodynamic Therapy In The Treatment Of Periodontitis

Periodontitis is a chronic infectious disease caused by dental plaque.Currently,conventional treatment of periodontitis have an unsatisfactory effect due to the complex anatomy of teeth and antibiotic resistance.Photodynamic therapy?PDT?is a physical treatment combined with light,photosensitizers and oxygen molecules,which has significant therapeutic effects on various diseases such as cancer,oral diseases and skin diseases,and can overcome the shortcomings in the current treatment of periodontitis.Toluidine blue O?TBO?as a photosensitizer have been widely used in antimicrobial photodynamic therapy.However,there are not a dosage form containing photosensitizers applied in oral treatment at present.Therefore,the development of a dosage form containing photosensitizer is the key to the successful application of photodynamic therapy in the treatment of periodontitis.Objective:The aim of this study was to develop TBO hydrogel for the treatment of periodontitis by in vitro antibacterial test.In vitro antibacterial test of clinical periodontal pathogen and rat periodontal model were used to verify the therapeutic effect of the TBO hydrogel.Methods:In this study,with the antibacterial activity as reference index,optimization of TBO hydrogel formulations and light treatment time.Then,study of stability?appearance,pH value and viscosity?of optimized TBO hydrogel,in vitro drug release and the effects on periodontal pathogens.Finally,study of PDT with optimum TBO hydrogel for periodontal disease in experimental rat periodontal model.Results:The results showed that:?1?In the single factor experiments,with the antibacterial activity as reference index,the optimal formulations are carbomer 934 as gel matrix,carbomer concentration of 3%?w/v?,TBO concentration of 0.1 mg/mL and the quality ratio of NaOH and carbomer of 0.4?w/w?.The optimal light treatment time are 40 s.?2?In the response surface methodology experiments,with the antibacterial activity as reference index,the optimal formulations are carbomer concentration of 3%?w/v?,TBO concentration of 0.1 mg/mL and the quality ratio of NaOH and carbomer of 0.4?w/w?.PDT with optimal TBO hydrogel exhibits stronger antibacterial activity against Staphylococcus aureus,Escherichia coli,the log-transformed of CFU mL^-1 decreased from 8.21,8.47 to 0.84,1.26 respectively.?3?In the stability studies,the optimal TBO hydrogels stored at 4?,25?and40?,respectively,have no significant change in appearance,pH and viscosity.It can be considered to be stable.?4?In vitro drug release studies,a rapid release TBO from the optimal TBO hydrogel was found.TBO hydrogel released approximately 50%of TBO in 4 h.After 6 h,the release of TBO reaches a balance.?5?In vitro anti-periodontal-pathogen test,PDT with optimal TBO hydrogel has significant antibacterial effect.?6?In the animal experiments,PDT with optimal TBO hydrogel has significant therapeutic effect on experimental rat periodontal disease model.And its curative effect was better than local antibiotics and systemic antibiotics treatment.More importantly,this method is more safe and effective,no drug resistance.Conclusion:In summary,PDT with TBO hydrogel exhibits stronger antibacterial activity against Staphylococcus aureus,Escherichia coli and periodontal pathogen in this paper.TBO hydrogel has strong stability and can release TBO quickly.PDT with optimal TBO hydrogel has significant therapeutic effect on experimental rat periodontal disease model.Therefore,this study provides a theoretical basis for the clinical trials of PDT with TBO hydrogel in the treatment of periodontitis.