Development of combined therapy of metronidazole and ibuprofen using in situ microgels for the treatment of periodontitis

Abstract

This study aimed to develop thermosensitive in-situ microgels loaded with the antimicrobial agent metronidazole (MTN) and the nonsteroidal anti-inflammatory drug ibuprofen (IBU) as adjunctive therapy for periodontitis. The MTN-IBU microgels were prepared by combining IBU-Microemulsions with MTN solution prepared with Pluronic® F127 (F127) hydrogel. The effect of various cosolvents and Pluronic F68 (F68) on the thermo-rheological properties (sol-gel transition temperature (Tsol→gel), viscosity, and viscoelastic properties) of MTN-IBU microgels was studied. The physicochemical properties of microgels were characterized by Fourier transform infrared (FTIR) and differential scanning calorimetry (DSC). The in vitro release and stability studies of microgels were investigated. An HPLC method was developed for the simultaneous quantification of MTN and IBU. Results showed that microgels were thermosensitive exhibiting Tsol→gel of 25–37 °C, pseudoplastic flow, and viscoelastic properties. The thermo-rheological properties of microgels were dependent on the concentration of F127, IBU-Microemulsion, cosolvents, and F68. Stability studies demonstrated that the thermo-rheological properties of microgels decreased after six months, except microgels containing F68 that were able to maintain their strength and undergo the phase transition. Microgels provided a complete MTN release after 8 h and a sustained IBU release for 24–48 h. This study highlighted the significance of in-situ microgels for delivering a combined therapy of MTN and IBU using two drug delivery systems (IBU-microemulsion and F127 sol) and the ability to modulate the thermo-rheological properties of microgels via the addition of various cosolvents and F68 to F127-based microgels as potential platforms for periodontitis.