Periodontal diseases are local bacterial infections that cause inflammation in periodontal (gum) tissues, significantly impacting a patient’s quality of life. Current clinical treatment, such as scaling and root planing combined with antibiotics, shows drawbacks, including antibiotic resistance. The potential of plant-derived bioactives with antimicrobial properties has led to growing interest in the biomedical field. Mānuka oil, an essential oil derived from the Leptospermum scoparium plant, is a potential candidate with known antibacterial and anti-inflammatory properties. Formulation of natural oils for delivery, sustained release, and substantivity in the oral environment is challenging. The integration of nanoencapsulation technology offers the potential to prolong the release time, as well as enhance biocompatibility and address the current therapeutic requirements. Microfluidics enables precise nanoparticle synthesis, while chitosan, due to its antimicrobial activity, muco-adhesion, and biocompatibility, represents a promising encapsulation polymer. This paper aims to review antimicrobial essential oils and nanoencapsulation methods, highlighting the application of microfluidics in developing mānuka oil-loaded chitosan nanoparticles for local delivery in periodontal treatment.

Mānuka oil (MO) is derived from mānuka shrubs in New Zealand (NZ) and presents antimicrobial properties that may help combat antibiotic resistance. However, applications of MO are limited due to volatility, sensitivity to light and heat, and the complexity of controlled administration. We used ionic gelation to encapsulate MO and its derivative β-triketones (TK) within chitosan nanocarriers. Nanoparticles were characterised for morphology, chemical composition, encapsulation efficiency and release profile. Antimicrobial properties and biocompatibility were evaluated. Nanoparticles loaded with MO or TK were successfully synthesised with an average size of 331.5 nm (PDI 0.431) and 333.5 nm (PDI 0.503), respectively. Formulations showed positive zeta potentials, stability, high yield (1.5-1.8 g), as well as oil release over 24 h. Bactericidal effect was achieved at concentrations of 3.125-25.000 mg/ml, with no cytotoxic effect. This study has demonstrated the formulation of MO and TK nanoparticles for potential applications in wound dressing, protective coating and targeted drug delivery.

Given the need for effective antimicrobial delivery to enhance the therapeutic efficacy of scaling and root planning (SRP) in periodontal treatment, this study aimed to develop a biocompatible and antimicrobial biogel incorporating mānuka oil or β-triketone-loaded chitosan nanoparticles, with comparable syringeability to a commercial periodontal gel (CURAPROX), as an adjunctive approach to SRP. Mānuka oil and β-triketone-loaded chitosan nanoparticles were produced using microfluidics and incorporated into a carboxymethyl cellulose (CMC) biogel. Rheological properties, including viscosity and frequency sweep, were optimized to match CURAPROX. Syringeability was evaluated by measuring the extrusion peak force. Nanoparticle distribution in the gel matrix was visualized using scanning electron microscopy (SEM). Antimicrobial activity of the nanoparticle-gel composites was assessed against Streptococcus mutans, Aggregatibacter actinomycetemcomitans and Fusobacterium nucleatum, and biocompatibility was evaluated on human gingival fibroblasts. Retention of the optimized formulation was further compared with CURAPROX in an in vitro periodontal pocket model simulating periodontitis. The optimized nanoparticle-gel composites exhibited viscosities between 60 and 65 Pa·s, comparable to CURAPROX, and extrusion peak force below 30 N, within syringeability limits. The mānuka oil and β-triketone-loaded chitosan nanoparticles demonstrated strong antimicrobial activity against periodontitis-associated bacteria, while maintaining good gingival fibroblast viability. In the in vitro periodontal pocket model, retention of the biogel was comparable to CURAPROX under periodontitis-mimicking conditions. This study demonstrates the successful synthesis of CMC biogel incorporating mānuka oil and β-triketone-loaded chitosan nanoparticles with comparable physiochemical and handling properties to commercial periodontal gel. The formulation highlights potential for localized antimicrobial delivery as an adjunctive therapy to SRP in periodontal treatment.

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 (Created by BioRender).