The goal of this proposal is to develop nitric oxide releasing dendrimers to inhibit biofilm based periodontopathogens and associated periodontal disease. The rationale for pursuing this work is based on nitric oxide's broad spectrum antimicrobial activity, rapid diffusion through biofilms, short half-life (thus imparting local acton) and physiological role in the immune response to pathogens. The use of a macromolecular NO release scaffold enables us to maximize bactericidal activity while minimizing the cytotoxic impact on healthy oral cells and tissue. We will study the influence of dendrimer size/molecular weight, charge, exterior functionality, and NO release properties on pathogenic plaque bacteria killing. We will systematically study both dendrimer and nitric oxide penetration into in vitro models of oral plaque biofilms as a function of biofilm composition, maturity and mass. An established murine model for periodontal infection will be employed to evaluate how dendrimer composition and nitric oxide release influence inflammation, host immune response, and biofilm eradication.

Public Health Relevance

The goal of this proposal is to study the efficacy of exogenous nitric oxide derived from dendrimers to prevent and treat periodontal disease. Our hypothesis is that localized nitric oxide delivery to periodontal pockets will significantly reduce microbial burden and eradicate dental plaque biofilms that cause periodontal disease. In addition to evaluating anti-biofilm utility and cytotoxicity, we will study the associated physiological response to dendrimers and nitric oxide in an established murine model of infection that mimics the subgingival biofilms characteristic of periodontal disease.

Agency
National Institute of Health (NIH)
Institute
National Institute of Dental & Craniofacial Research (NIDCR)
Type
Research Project (R01)
Project #
5R01DE025207-03
Application #
9261511
Study Section
Nanotechnology Study Section (NANO)
Program Officer
Lumelsky, Nadya L
Project Start
2015-07-02
Project End
2020-04-30
Budget Start
2017-05-01
Budget End
2018-04-30
Support Year
3
Fiscal Year
2017
Total Cost
$278,922
Indirect Cost
$89,746
Name
University of North Carolina Chapel Hill
Department
Chemistry
Type
Schools of Arts and Sciences
DUNS #
608195277
City
Chapel Hill
State
NC
Country
United States
Zip Code
27599
Yang, Lei; Feura, Evan S; Ahonen, Mona Jasmine R et al. (2018) Nitric Oxide-Releasing Macromolecular Scaffolds for Antibacterial Applications. Adv Healthc Mater 7:e1800155
Suchyta, Dakota J; Soto, Robert J; Schoenfisch, Mark H (2017) Selective monophosphorylation of chitosan via phosphorus oxychloride. Polym Chem 8:2552-2558
Backlund, Christopher J; Worley, Brittany V; Schoenfisch, Mark H (2016) Anti-biofilm action of nitric oxide-releasing alkyl-modified poly(amidoamine) dendrimers against Streptococcus mutans. Acta Biomater 29:198-205
Backlund, C J; Worley, B V; Sergesketter, A R et al. (2015) Kinetic-dependent Killing of Oral Pathogens with Nitric Oxide. J Dent Res 94:1092-8