Nanoparticle carrier co-delivery of complementary antibiofilm drugs abrogates dual species cariogenic biofilm formation in vitro

纳米粒子载体共同递送互补的抗生物膜药物可在体外消除双物种致龋生物膜的形成

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作者:Guilherme Roncari Rocha, Kenneth R Sims Jr, Baixue Xiao, Marlise I Klein, Danielle S W Benoit

Aim

This study aimed to prevent the formation of S. mutans and C. albicans biofilms by exploiting pH-sensitive nanoparticle carriers (NPCs) with high affinity to exopolysaccharides to increase the substantivity of multi-targeted antibiofilm drugs introduced topically in vitro.

Background

Dental caries is a multifactorial disease caused by pathogenic biofilm. In particular, Streptococcus mutans synthesizes biofilm exopolysaccharides, while Candida albicans is associated with the development of severe carious lesions.

Conclusion

Complementary antibiofilm drug-NPC treatments prevented biofilm formation by targeting critical virulence factors of acidogenicity and exopolysaccharides synthesis.

Methods

Dual-species biofilms were grown on saliva-coated hydroxyapatite discs with sucrose. Twice-daily, 1.5 min topical treatment regimens of unloaded and drug-loaded NPC were used. Drugs included combinations of two or three compounds with distinct, complementary antibiofilm targets: tt-farnesol (terpenoid; bacterial acid tolerance, fungal quorum sensing), myricetin (flavonoid; exopolysaccharides inhibitor), and 1771 (lipoteichoic acid inhibitor; bacterial adhesion and co-aggregation). Biofilms were evaluated for biomass, microbial population, and architecture.

Results

NPC delivering tt-farnesol and 1771 with or without myricetin completely prevented biofilm formation by impeding biomass accumulation, bacterial and fungal population growth, and exopolysaccharide matrix deposition (vs. control unloaded NPC). Both formulations hindered acid production, maintaining the pH of spent media above the threshold for enamel demineralization. However, treatments had no effect on pre-established dual-species biofilms.

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