Assessment of CafA Targeted BAR-Encapsulated Nanoparticles against Oral Biofilms

• Main Authors: Hetal Desai (Author), Mohamed Y. Mahmoud (Author), Jinlian Tan (Author), Farnaz Minooei (Author), Donald R. Demuth (Author), Jill M. Steinbach-Rankins (Author)
• Format: Book
• Published: MDPI AG, 2020-09-01T00:00:00Z.
• Subjects: article
• Online Access: Connect to this object online.

Summary

<i>Porphyromonas gingivalis</i> adherence to <i>Streptococcus gordonii</i> is a crucial initial event that facilitates the colonization of <i>P. gingivalis</i>, a key pathogen in periodontal disease. As such, blocking these early interactions may present a potential avenue to limit <i>P. gingivalis</i> colonization. Nanoparticles encapsulating a synthetic peptide BAR (BAR-encapsulated NPs) inhibit <i>P. gingivalis</i>/<i>S. gordonii</i> 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, <i>Actinomyces oris</i>. We demonstrate that the targeting moiety, CafA, enhances NP binding and exhibits specificity of adherence to <i>S. gordonii</i>, 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 <i>P. gingivalis</i>/<i>S. gordonii</i> 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 <i>P. gingivalis</i> preferred niches.

Item Description

10.3390/pharmaceutics12090835
1999-4923