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Article

Assessment of CafA Targeted BAR-Encapsulated Nanoparticles against Oral Biofilms

1
Department of Oral Immunology and Infectious Diseases, University of Louisville School of Dentistry, Louisville, KY 40202, USA
2
Department of Microbiology and Immunology, University of Louisville School of Medicine, Louisville, KY 40202, USA
3
Department of Pharmacology and Toxicology, University of Louisville School of Medicine, Louisville, KY 40202, USA
4
Center for Predictive Medicine, University of Louisville, Louisville, KY 40202, USA
5
Department of Toxicology, Forensic Medicine and Veterinary Regulations, Faculty of Veterinary Medicine, Cairo University, Giza 12211, Egypt
6
Department of Chemical Engineering, University of Louisville Speed School of Engineering, Louisville, KY 40202, USA
7
Department of Bioengineering, University of Louisville Speed School of Engineering, Louisville, KY 40202, USA
*
Authors to whom correspondence should be addressed.
These authors contribute equally to this paper.
Pharmaceutics 2020, 12(9), 835; https://doi.org/10.3390/pharmaceutics12090835
Received: 27 July 2020 / Revised: 13 August 2020 / Accepted: 26 August 2020 / Published: 1 September 2020
(This article belongs to the Special Issue Advances in Oral and Buccal Drug Delivery)
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. View Full-Text
Keywords: periodontal disease; Porphyromonas gingivalis; Streptococcus gordonii; oral biofilm; nanoparticles; peptide delivery; CafA protein; oral delivery; targeted oral therapy periodontal disease; Porphyromonas gingivalis; Streptococcus gordonii; oral biofilm; nanoparticles; peptide delivery; CafA protein; oral delivery; targeted oral therapy
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MDPI and ACS Style

Desai, H.; Mahmoud, M.Y.; Tan, J.; Minooei, F.; Demuth, D.R.; Steinbach-Rankins, J.M. Assessment of CafA Targeted BAR-Encapsulated Nanoparticles against Oral Biofilms. Pharmaceutics 2020, 12, 835. https://doi.org/10.3390/pharmaceutics12090835

AMA Style

Desai H, Mahmoud MY, Tan J, Minooei F, Demuth DR, Steinbach-Rankins JM. Assessment of CafA Targeted BAR-Encapsulated Nanoparticles against Oral Biofilms. Pharmaceutics. 2020; 12(9):835. https://doi.org/10.3390/pharmaceutics12090835

Chicago/Turabian Style

Desai, Hetal, Mohamed Y. Mahmoud, Jinlian Tan, Farnaz Minooei, Donald R. Demuth, and Jill M. Steinbach-Rankins 2020. "Assessment of CafA Targeted BAR-Encapsulated Nanoparticles against Oral Biofilms" Pharmaceutics 12, no. 9: 835. https://doi.org/10.3390/pharmaceutics12090835

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