Antimicrobial and Anti-inflammatory Potential of Thermoresponsive In situ Gel Loaded with Metronidazole Microsponges for Localized Treatment of Periodontitis

Abstract

Periodontitis is an inflammatory disease that penetrates deeply into the tissues, causing loss of alveolar bone and supporting connective tissues. Severe periodontal diseases are estimated to affect around 19% of the global adult population, representing more than 1 billion cases worldwide. Metronidazole (MTZ) is frequently used to inhibit anaerobic bacteria in periodontal disease. This study aimed to fabricate MTZ-eudragit microsponges (MSPs) and then loading them into in situ gel to evaluate its sustained local action in the buccal cavity. To optimize MTZ- MSPs, different variables such as drug: polymer ratio, polymer: solvent ratio and stirring rate were studied. In vitro characterization of MSPs, such as thermal behavior, surface morphology, particle size and drug release, were studied. The optimized MSPs were spherical with numerous pores on the surface (sponge-like particles). These optimized MSPs also showed entrapment efficiency (85 ± 1%), mean particle size of 44 ± 1 μm (PDI 0.2 ± 0.1) and sustained drug release (57 ± 1% through 12 h). The optimized MSPs were then incorporated into a thermoresponsive in situ gel (20% PF-127/2% PF-68/0.5% HPMC). The MSPs-containing in situ gel was free flowing at room temperature and transformed into a gel in the buccal cavity, retarding drug release and enhancing the mucoadhesion and antibacterial activity. Finally, in vivo studies on rats revealed that this gel is an effective and innovative approach to treating periodontitis. In conclusion, MSPs-loaded in situ gel represents a promising vehicle for MTZ to treat periodontitis.