Development and optimization of antimicrobial β-triketone-loaded chitosan nanoparticles for periodontal therapy

Abstract Periodontal disease is a bacterial infection leading to the progressive destruction of soft and hard oral tissues. Current clinical treatment involves scaling and root planing (SRP), combined with adjunctive therapies, such as the application of antibacterial reagents. Mānuka oil, derived from Leptospermum scoparium , a native plant in New Zealand and Australia, exhibits broad-spectrum antibacterial activity mainly attributed to its β-triketone compounds. However, due to the limitations, including low solubility and strong volatility, clinical translation of mānuka oil and β-triketones is limited. Given the biocompatible, antimicrobial, and mucoadhesive properties of chitosan, this study aimed to synthesize mānuka oil and β-triketone-loaded chitosan nanoparticles to achieve sustained release and enhanced antimicrobial efficacy, supporting their therapeutic potential as a natural and antibiotic-free alternative for treating bacterial infections, especially in periodontal disease. Mānuka oil and β-triketone-loaded chitosan nanoparticles were synthesized using a microfluidic platform with the average size of 253.0 nm (polydispersity index (PDI): 0.421) and 196.5 nm (PDI: 0.446), respectively. Encapsulation techniques enabled prolonged oil release over 24 h, with effective antimicrobial activity against Staphylococcus aureus , Streptococcus mutans , Aggregatibacter actinomycetemcomitans , and Fusobacterium nucleatum , and good in vitro biocompatibility with human mesenchymal stem cells. Overall, the presented study highlights a phytotherapy using nanoparticles for the local delivery of mānuka oil and β-triketones. These antimicrobial formulations provide potential as an adjunct to SRP in periodontal treatment and broader bacterial infections. Key points • Periodontal disease arises from the accumulation of dental plaque. • Mānuka oil and its β-triketone compounds exhibit strong antimicrobial activity. • Microfluidics-produced nanoparticles show potential as antibiotic-free adjuncts. Graphical abstract (Created by BioRender).