Metronidazole-Loaded Porous Matrices for Local Periodontitis Treatment: In Vitro Evaluation and In Vivo Pilot Study

Abstract

Periodontal therapy focuses on thorough removal of subgingival calculus and plaque products followed by the smoothing out of root surfaces. However, such conventional mechanotherapeutic approaches are inefficient with regard to microbial biofilm elimination from the space between the root and deep periodontal pockets. Therefore, local chemotherapeutic agents need to be applied. Local antimicrobial treatment is also considered a safer treatment, as it avoids systemic complications related to drug application. In this study, porous matrices consisting of gelatin (GE) and cellulose derivatives (carboxymethylcellulose (CMC) and hydroxyethyl cellulose (HEC)) were loaded with antimicrobial drug metronidazole (MTZ). The matrices’ structural morphology, physiochemical properties, swelling and degradation ratio, mechanical properties, and MTZ release from the matrices were analyzed. Additionally, cytotoxicity tests for fibroblast and osteoblast cell cultures (L929 and U2-OS, respectively) and antimicrobial activity assessments of MTZ-loaded matrices against anaerobic Bacteroides sp. Bacteria were performed. Finally, clinical application of HEC matrices into periodontal pockets was conducted. The applied matrices showed a high antibacterial efficacy and a moderate cytotoxicity in vitro. The clinical application of HEC dressings corresponded with the decrease of periodontal pockets’ depth and bleeding observed 1 month after a single application. The presented results show that intra-pocket application of metronidazole using manufactured matrices may serve not only as a support for a standard treatment in periodontal practice but also as an alternative to systemic drug administration in this setting. Clinical data were analyzed using a nonparametric Friedman’s ANOVA for dependent trials.

Keywords

• metronidazole
• cellulose derivatives
• periodontal
• clinical pilot study