Abstract
Porphyromonas gingivalis adherence to Streptococcus gordonii is a crucial initial event that facilitates the colonization of P. gingivalis, a key pathogen in periodontal disease. As such, blocking these early interactions may present a potential avenue to limit P. gingivalis colonization. Nanoparticles encapsulating a synthetic peptide BAR (BAR-encapsulated NPs) inhibit P. gingivalis/S. gordonii 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, Actinomyces oris. We demonstrate that the targeting moiety, CafA, enhances NP binding and exhibits specificity of adherence to S. gordonii, 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 P. gingivalis/S. gordonii 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 P. gingivalis preferred niches.
Highlights
Periodontitis is the inflammation of tooth-supporting structures, caused by dental plaque, which leads to the destruction of periodontal ligament and alveolar bone
After 12 h, this resulted in a 12.4-fold higher concentration of CafAmodified NPs bound to S. gordonii (Figure 5B). These results indicate that the ratio of coaggregation factor A (CafA)-modified to unmodified NPs bound to S. gordonii was maintained after the first wash and suggest that the targeting moiety, CafA, improves the binding efficiency of unmodified NPs and enhances their rPehtearnmtaicoenutibcsy2s0i2g0,n1i2f,ic8a35ntly increasing the concentration of CafA-modified NPs that bind to S. gor1d3oonfi2i2 relative to unmodified NPs
Our results demonstrate that CafA-modified NPs exhibit high binding and specificity to receptor polysaccharides (RPS)-expressing commensal bacteria, relative to other bacteria including S. mutans, P. gingivalis, and A. actinomycetemcomitans, and remain bound to S. gordonii, while exerting functionality in a dual-species biofilm for up to 12 h
Summary
Periodontitis is the inflammation of tooth-supporting structures, caused by dental plaque, which leads to the destruction of periodontal ligament and alveolar bone. From 2009 to 2014, 42% of adults (age > 30 years) in the United States, were diagnosed with periodontal disease. Of these patients, 7.8% had advanced periodontitis [1]. Antibiotic effectiveness in the treatment of periodontitis is often limited, due to compromised penetration of antibiotics through the oral biofilm, increased drug resistance of the biofilm relative to planktonic bacteria, reduced cellular activity of bacteria within the biofilm, and prevalence of resistant pathogens in the subgingival microflora [7,8]. Long-term, indiscriminate use of antibiotics in the treatment of periodontal disease may lead to adverse side effects such as toxicity, allergies, alteration of gut microflora, and increased antimicrobial resistance [10]. There is a compelling need to develop novel, targeted, therapeutic approaches beyond antibiotics for the prevention and treatment of periodontal disease
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