Combination of metronidazole and green tea extract-loaded nanoparticles: Formulation, optimization, in vitro and ex vivo study for the treatment of periodontal disease.

Background: The study aimed to enhance the efficacy of periodontal treatment through the development of dual drug-loaded nanoparticles (NPs) of metronidazole (MET) and green tea extract (GTE).

Materials and methods: The NPs were prepared by solvent displacement, optimized by central composite rotatable design. The particle size, polydispersity index (PDI), and entrapment efficiency were assessed. The cell viability was assessed using the L929 mouse fibroblast cell lines. In addition, texture analysis, flux, and permeability coefficient of MET and GTE gel were measured. Minimum inhibitory concentration (MIC) was assessed on isolates obtained from periodontal patients. Hen's egg test-chorioallantoic membrane (HET-CAM) study was conducted to assess the irritability and tolerability of NPs.

Results: The optimized NPs had a mean particle size of 171.0 ± 49.34 nm, a mean PDI of 0.383 ± 0.907, and a high entrapment efficacy of 89% ± 0:25%. Cell viability assay demonstrated 93.8% viability on mouse fibroblast cell lines. Texture analysis of NP-loaded gel showed high cohesiveness, less firmness, and consistency. The flux and permeability coefficient of MET and GTE was found to be 9.084 µg/h/cm², 7.8005 µg/h/cm², 0.0036 cm/h, and 0.0039 cm/h. The confocal study showed an increase in the depth of NPs due to their nanosized particles. The MIC values were 400 µg/mL for MET and 500 µg/mL for GTE against periodontal isolates. HET-CAM study illustrates that the NPs are secure, nonirritating, and well tolerated for periodontal disease.

Conclusions: Dual-drug-loaded NPs exhibited significant antimicrobial activity against periodontal pathogens and demonstrated promising potential to enhance the clinical outcomes of periodontal therapy.