Polymer vesicles for the delivery of inhibitors of cariogenic biofilm.

OBJECTIVES: The goal of this study is to develop a novel drug delivery platform for the pH-responsive delivery of biofilm inhibitors as a potential avenue to prevent and treat dental caries. METHODS: Biofilm and growth inhibition assays were performed in polystyrene microtiter 96-well plates. Docking analysis was performed using the reported GtfB + HA5 co-crystal structure (PDB code: 8fg8) in SeeSAR 13.0.1 software. Polymersome vesicles were assembled from poly(N-vinylpyrrolidone)(8)-block-poly(dimethylsiloxane)(64)-block-poly(N-vinylpyrrolidone)(8) (PVPON(8)-PDMS(64)-PVPON(8)) triblock copolymer using a nanoprecipitation method. Microbiome analysis of biofilm inhibitors and the in vivo drug release and antivirulence activities of polymersome encapsulated inhibitors have been carried out in a S. mutans induced rat caries model. RESULTS: Biofilm inhibitors for HA5 and HA6 have shown species-specific selectivity towards S. mutans and the ability to preserve the oral microbiome in a S. mutans induced dental caries model. The inhibitors were encapsulated into pH-responsive block copolymer vesicles to generate polymersome-encapsulated biofilm inhibitors, and their biofilm and growth inhibitory activities against S. mutans and representative strains of oral commensal streptococci have been assessed. A 4-week treatment of S. mutans UA159 infected gnotobiotic rats with 100 microM of polymersome-encapsulated biofilm inhibitor, PEHA5 showed significant reductions in buccal, sulcal, and proximal caries scores compared to an untreated control group. SIGNIFICANCE: Taken together, our data suggests that the biofilm-selective therapy using the polymersome-encapsulated biofilm inhibitors is a viable approach for the prevention and treatment of dental caries while preserving the oral microbiome.