Scutellaria baicalensis (SB) is a traditional Chinese medicine for treating infectious and inflammatory diseases. Our recent study shows potent antibacterial effects of nanoparticle-encapsulated chlorhexidine (Nano-CHX). Herein, we explored the synergistic effects of the nanoparticle-encapsulated SB (Nano-SB) and Nano-CHX on oral bacterial biofilms. Loading efficiency of Nano-SB was determined by thermogravimetric analysis, and its releasing profile was assessed by high-performance liquid chromatographyusing baicalin (a flavonoid compound of SB) as the marker. The mucosal diffusion assay on Nano-SB was undertaken in a porcine model. The antibacterial effects of the mixed nanoparticles (Nano-MIX) of Nano-SB and Nano-CHX at 9:1 (w/w) ratio were analyzed in both planktonic and biofilm modes of representative oral bacteria. The Nano-MIX was effective on the mono-species biofilms of Streptococcus (S.) mutans, S. sobrinus, Fusobacterium (F.) nucleatum, and Aggregatibacter (A.) actinomycetemcomitans (MIC 50 μg/mL) at 24 h, and exhibited an enhanced effect against the multi-species biofilms such as S. mutans, F. nucleatum, A. actinomycetemcomitans, and Porphyromonas (P.) gingivalis (MIC 12.5 μg/mL) at 24 h that was supported by the findings of both scanning electron microscopy (SEM) and confocal scanning laser microscopy (CLSM). This study shows enhanced synergistic antibacterial effects of the Nano-MIX on common oral bacterial biofilms, which could be potentially developed as a novel antimicrobial agent for clinical oral/periodontal care.

Oral mucosa as the front-line barrier in the mouth is constantly exposed to a complex microenvironment with multitudinous microbes. In this study, the interactions of mesoporous silica nanoparticles (MSNs) with primary human gingival epithelial cells were analyzed for up to 72 h, and their diffusion capacity in the reconstructed human gingival epithelia (RHGE) and porcine ear skin models was further assessed at 24 h. It was found that the synthesized fluorescent mesoporous silica nanoparticles (RITC-NPs) with low cytotoxicity could be uptaken, degraded, and/or excreted by the human gingival epithelial cells. Moreover, the RITC-NPs penetrated into the stratum corneum of RHGE in a time-dependent manner, while they were unable to get across the barrier of stratum corneum in the porcine ear skins. Consequently, the penetration and accumulation of RITC-NPs at the corneum layers of epithelia could form a “nanocoating-like barrier”. This preliminary proof-of-concept study suggests the feasibility of developing nanoparticle-based antimicrobial and anti-inflammatory agents through topical application for oral healthcare.