Desai Hetal, Mahmoud Mohamed Y, Tan Jinlian, Minooei Farnaz, Demuth Donald R, Steinbach-Rankins Jill M
Department of Oral Immunology and Infectious Diseases, University of Louisville School of Dentistry, Louisville, KY 40202, USA.
Department of Microbiology and Immunology, University of Louisville School of Medicine, Louisville, KY 40202, USA.
Pharmaceutics. 2020 Sep 1;12(9):835. doi: 10.3390/pharmaceutics12090835.
adherence to is a crucial initial event that facilitates the colonization of , a key pathogen in periodontal disease. As such, blocking these early interactions may present a potential avenue to limit colonization. Nanoparticles encapsulating a synthetic peptide BAR (BAR-encapsulated NPs) inhibit / biofilm formation 1.8-fold more potently relative to free BAR. However, BAR-encapsulated NPs, like many orally delivered formulations, may benefit from a strategy that improves their retention in an open flow environment. Here, we sought to enhance the efficacy of BAR-encapsulated NPs by modifying their surfaces with coaggregation factor A (CafA), a fimbrial protein expressed by the early colonizer, . We demonstrate that the targeting moiety, CafA, enhances NP binding and exhibits specificity of adherence to , relative to other oral bacterial species. Furthermore, CafA-modified NPs release inhibitory concentrations of BAR for 12 h, a time frame relevant to oral dosage form delivery. Lastly, CafA-modified NPs potently inhibit / biofilm formation for up to 12 h and are non-toxic at therapeutically-relevant concentrations. These results suggest that CafA-modified NPs represent a novel and efficacious delivery vehicle for localized, targeted delivery of BAR to preferred niches.
黏附于牙龈卟啉单胞菌是促进其定植的关键初始事件，牙龈卟啉单胞菌是牙周病的关键病原体。因此，阻断这些早期相互作用可能是限制牙龈卟啉单胞菌定植的潜在途径。包裹合成肽BAR的纳米颗粒（BAR包裹的纳米颗粒）抑制牙龈卟啉单胞菌生物膜形成的能力比游离BAR强1.8倍。然而，与许多口服制剂一样，BAR包裹的纳米颗粒可能受益于一种能提高其在开放流动环境中滞留率的策略。在这里，我们试图通过用共聚凝集因子A（CafA）修饰BAR包裹的纳米颗粒表面来提高其功效，CafA是早期定植菌血链球菌表达的一种菌毛蛋白。我们证明，与其他口腔细菌种类相比，靶向部分CafA增强了纳米颗粒的结合，并表现出对血链球菌黏附的特异性。此外，CafA修饰的纳米颗粒在12小时内释放出抑制浓度的BAR，这与口服剂型给药的时间框架相关。最后，CafA修饰的纳米颗粒在长达12小时内有效抑制牙龈卟啉单胞菌生物膜形成，并且在治疗相关浓度下无毒。这些结果表明，CafA修饰的纳米颗粒是一种新型且有效的递送载体，可将BAR局部靶向递送至血链球菌的优选生态位。
