pH-Responsive Microspheres Encapsulating Metronidazole or N-Phenacylthiazolium Bromide Modulate Periodontitis Progression

Objectives: Systemically administered antibiotics or advanced glycation end-product breaker have been proven to be effective for treating periodontitis. However, adverse systemic effects and resistance may occur. Local delivery via a controlled-release device appears to be a feasible solution. This study was designed to examine the therapeutic potential of pH-responsive microspheres encapsulating metronidazole (MTZ) and N-Phenacylthizolium bromide (PTB), an AGE breaker, in treating experimental periodontitis.
Methods: pH-responsive Chitosan/PLGA microspheres loaded with MTZ or PTB were fabricated respectively, and the dimension as well as the drug release profile was characterized in vitro. Twelve Sprague-Dawley rats were utilized and divided into 4 groups with a split-mouth design, including (a) Group CT: control group without microspheres delivery; (b) Group MP: microspheres alone; (c) Group MT: microspheres encapsulating MTZ (d) Group PB: microspheres encapsulating PTB. Experimental periodontitis was induced by submerging a 4-0 silk in the gingival sulcus of maxillary second molars in all animals, and microspheres were subgingivally delivered after 7 days of silk placement. Periodontal bone loss (PBL) was evaluated by micro-computed tomography on the baseline and 0, 4 and 21 days after microspheres delivery. The histology as well as the ratio of inflammatory cells to total cells were assessed on 21 days after drug delivery.
Results: The microspheres were 6.10±1.80μm in diameter, with sustained release of drug over a period of one week. PBL apparently decrease inboth groups MT and PB relative to group MP on day 4, whereas slightly increase of PBL in group MT was noted on day 21. Both groups MT and PB showed significant decrease in inflammatory cell infiltration relative to group MP on day 21 (p<0.05 & p<0.01).
Conclusions: pH-responsive microspheres encapsulating MTZ and PTB effectively reduce inflammation, and PTB appears to resist further periodontal breakdown in experimental periodontitis.