Metronidazole‐Loaded Cyclodextrin Nanogels for Antibacterial Therapy and Microbiota Regulation in Periodontitis

Abstract In this study, a methacrylamide β‐cyclodextrin‐based nanogel (MACD nGel) is developed to load the antimicrobial drug Metronidazole (MNZ) for topical delivery for the treatment of periodontitis. The developed MACD nGel is synthesized by free radical polymerization and successfully loaded with MNZ. The nGel/MNZ system is shown to be effective against the main causative organisms of periodontitis, Porphyromonas gingivalis ( P. gingivalis ) and Fusobacterium nucleatum ( F. nucleatum ), and shows significant bacteriostatic effects and good cytocompatibility. In animal studies, the topical application of nGel/MNZ significantly attenuates the inflammatory response in periodontitis, reduces the expression of key inflammatory factors interleukin 1 beta (IL‐1β) and tumor necrosis factor alpha (TNF‐α), and improves the balance of the microbial composition of gingival crevicular fluid (GCF). The study demonstrates that cyclodextrin nanogel (nGel) loaded with metronidazole not only provides an efficient drug delivery route but also has potential clinical applications and offers a novel strategy for the local treatment of periodontitis.