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

**Authors:** Yanjing Ji, Ruichen Zhang, Dongyi Xu, Patrick C. A. van der Wel, Alessia Lasorsa, Guotai Li, Fangze Guo, Qihui Zhou, Patrick van Rijn

PMC · DOI: 10.1002/adhm.202502965 · 2025-10-28

## TL;DR

A new nanogel system is developed to deliver metronidazole for treating periodontitis, reducing inflammation and improving microbial balance.

## Contribution

A methacrylamide β-cyclodextrin-based nanogel is introduced for efficient topical delivery of metronidazole in periodontitis treatment.

## Key findings

- The MACD nGel effectively delivers metronidazole and targets key periodontitis-causing bacteria.
- Topical application of nGel/MNZ reduces inflammation and balances microbial composition in animal models.
- The system shows good cytocompatibility and bacteriostatic effects against P. gingivalis and F. nucleatum.

## 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.

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. It is demonstrated that cyclodextrin nanogel (nGel) loaded with metronidazole provides an efficient drug delivery route but also has potential clinical applications and offers a novel strategy for the local treatment of periodontitis.

## Linked entities

- **Chemicals:** Metronidazole (PubChem CID 4173)
- **Diseases:** periodontitis (MONDO:0005076)
- **Species:** Porphyromonas gingivalis (taxon 837), Fusobacterium nucleatum (taxon 851)

## Full-text entities

- **Diseases:** Periodontitis (MESH:D010518), inflammatory (MESH:D007249)
- **Chemicals:** -cyclodextrin (MESH:D003505), MACD (-), methacrylamide (MESH:C045985), MNZ (MESH:D008795)
- **Species:** Porphyromonas gingivalis (species) [taxon 837], Fusobacterium nucleatum (species) [taxon 851]

## Figures

9 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12973357/full.md

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Source: https://tomesphere.com/paper/PMC12973357