Injectable Naringin-carrying Thermo-sensitive and pH-responsive Colloidal Hydrogel for Modulating Periodontitis

Objectives: Naringin is a naturally-derived polymethoxylated flavonoid compound with anti-inflammatory property, but the therapeutic value in treating periodontitis, a common inflammatory destruction of periodontium, remains undetermined. This study aimed at investigating the preclinical feasibility of naringin in modulating periodontitis via a thermo-gelling and pH-responsive injectable hydrogel.
Methods: The hydrogel was constituted by amphiphatic carboxymethyl-hexanoyl chitosan (CHC), beta glycerol-phosphate (b-GP), and glycerol, and naringin was encapsulated during the fabrication process. Gelation time at 4 and 37″C, and the release of naringin at pH5.5-7.4, were evaluated in vitro. Experimental periodontitis was created in rat maxillary molars and was treated with hydrogel alone (PH), hydrogel carrying naringin (PN), experimental periodontitis alone (PR), or was untreated (CT) in the induction or recovery phases. The treatment outcome was evaluated by micro-CT imaging and histology.
Results: The hydrogel was consistently flowable at 4°C but was rapidly gelling at 37°C, and the release of medicine was faster in pH 5.5-6.5 relative to pH 7.4 over a period of two weeks. In the induction phase of experimental periodontitis, significantly reduced periodontal bone level (p<0.05) and inflammation (p<0.05) relative to group PR was noted in group PN. However, in the recovery phase, inflammation was slightly reduced, and no obvious further promotion of periodontal bone level was noted in group PN.
Conclusions: Naringin combined with CHC-b-GP-glycerol hydrogel can be used to halt the induction of experimental periodontitis with favorable handling and inflammation-responsive characteristics, and the effect in the recovery phase appeared to be limited.