Abstract: Objective: To investigate the feasibility of thermosensitive gels with combined drug loading for the treatment of periodontitis. Methods: Phospholipid complexes, microspheres, and microemulsions of naringin were prepared using carrier dispersion technique. Subsequently, three thermosensitive in situ gels of naringin combined with berberine hydrochloride were prepared. The appearance, gelation temperature and time, drug loading capacity, in vitro drug release rate, antibacterial activity, and cell repair effects were compared. Results: All three thermosensitive gels were yellow transparent liquids at room temperature and gelled at approximately 37 ℃. The naringin microemulsion-berberine gel (NM-BGel) was demonstrated the shortest gelation time (57 s) and the highest drug loading capacity (0.98 mg for berberine hydrochloride and 13.72 mg for naringin). The drug release rate of berberine hydrochloride was 80% at 48 h, naringin was delayed and 80% at 200 h, which showed a time-segmented release mode. NM-BGel exhibited inhibitory effects on P. gingivalis and increased ALP activity in hPDLFs promoting their proliferation. Conclusion: The combined drug-loaded thermosensitive gel prepared based on microemulsion dispersion technology can achieve a time-segmented drug release and play antibacterial and cell repair functions in vitro over time. This provides experimental evidence for further research on local sustained drug delivery systems for periodontitis and comprehensive treatment of periodontitis.

Key words: naringin, berberine hydrochloride, thermosensitive gel, periodontitis, microemulsion