Polymer vesicles for the delivery of inhibitors of cariogenic biofilm.

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. 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) 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 µM of polymersome-encapsulated biofilm inhibitor, PEHA5 showed significant reductions in buccal, sulcal, and proximal caries scores compared to an untreated control group. 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.

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