Department of Pediatric Dentistry, Nihon University School of Dentistry at Matsudo, Chiba, Japan.
Biofilm Research Labs, Levy Center for Oral Health, School of Dental Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
Mol Oral Microbiol. 2022 Oct;37(5):218-228. doi: 10.1111/omi.12379. Epub 2022 Aug 4.
Streptococcus mutans and Candida albicans are frequently detected together in the plaque from patients with early childhood caries (ECC) and synergistically interact to form a cariogenic cross-kingdom biofilm. However, this biofilm is difficult to control. Thus, to achieve maximal efficacy within the complex biofilm microenvironment, nanoparticle carriers have shown increased interest in treating oral biofilms in recent years. Here, we assessed the anti-biofilm efficacy of farnesol (Far), a hydrophobic antibacterial drug and repressor of Candida filamentous forms, against cross-kingdom biofilms employing drug delivery via polymeric nanoparticle carriers (NPCs). We also evaluated the effect of the strategy on teeth enamel demineralization. The farnesol-loaded NPCs (NPC+Far) resulted in a 2-log CFU/mL reduction of S. mutans and C. albicans (hydroxyapatite disc biofilm model). High-resolution confocal images further confirmed a significant reduction in exopolysaccharides, smaller microcolonies of S. mutans, and no hyphal form of C. albicans after treatment with NPC+Far on human tooth enamel (HT) slabs, altering the biofilm 3D structure. Furthermore, NPC+Far treatment was highly effective in preventing enamel demineralization on HT, reducing lesion depth (79% reduction) and mineral loss (85% reduction) versus vehicle PBS-treated HT, while NPC or Far alone had no differences with the PBS. The drug delivery via polymeric NPCs has the potential for targeting bacterial-fungal biofilms associated with a prevalent and costly pediatric oral disease, such as ECC.
变形链球菌和白色念珠菌经常在早期儿童龋（ECC）患者的菌斑中同时检测到，并协同作用形成致龋跨界生物膜。然而，这种生物膜很难控制。因此，为了在复杂的生物膜微环境中实现最大疗效，近年来纳米颗粒载体在治疗口腔生物膜方面引起了越来越多的关注。在这里，我们评估了法尼醇（Far）作为一种疏水抗菌药物和白色念珠菌丝状形式抑制剂对跨界生物膜的抗生物膜功效，该药物通过聚合物纳米颗粒载体（NPC）进行药物输送。我们还评估了该策略对牙齿脱矿的影响。负载法尼醇的 NPC（NPC+Far）可使 S. mutans 和 C. albicans 的 CFU/mL 减少 2 个对数级（羟基磷灰石盘生物膜模型）。高分辨率共聚焦图像进一步证实，在 NPC+Far 处理后，人牙釉质（HT）平板上的 S. mutans 胞外多糖显著减少，微生物菌落变小，且白色念珠菌无菌丝形态，改变了生物膜的 3D 结构。此外，NPC+Far 处理在预防 HT 脱矿方面非常有效，与 PBS 处理的 HT 相比，其牙釉质深度（减少 79%）和矿物质损失（减少 85%）显著降低，而 NPC 或 Far 单独处理与 PBS 相比无差异。通过聚合物 NPC 进行药物输送有可能针对与流行且昂贵的儿科口腔疾病（如 ECC）相关的细菌-真菌生物膜。
