Antibacterial activity of nitric oxide-releasing carboxymethylcellulose against periodontal pathogens
Evan S. Feura
Department of Chemistry, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA
Search for more papers by this authorLei Yang
Department of Chemistry, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA
Search for more papers by this authorCorresponding Author
Mark H. Schoenfisch
Department of Chemistry, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA
Correspondence
Mark H. Schoenfisch, Department of Chemistry, University of North Carolina at Chapel Hill, CB 3290, Chapel Hill, NC 27599.
Email: [email protected]
Search for more papers by this authorEvan S. Feura
Department of Chemistry, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA
Search for more papers by this authorLei Yang
Department of Chemistry, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA
Search for more papers by this authorCorresponding Author
Mark H. Schoenfisch
Department of Chemistry, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA
Correspondence
Mark H. Schoenfisch, Department of Chemistry, University of North Carolina at Chapel Hill, CB 3290, Chapel Hill, NC 27599.
Email: [email protected]
Search for more papers by this authorAbstract
The prevalence of periodontal disease poses a significant global health burden. Treatments for these diseases, primarily focused on removal and eradication of dental plaque biofilms, are challenging due to limited access to periodontal pockets where these oral pathogens reside. Herein, we report on the development and characterization of nitric oxide (NO)-releasing carboxymethylcellulose (CMC) derivatives and evaluate their in vitro bactericidal efficacy against planktonic Porphyromonas gingivalis and Aggregatibacter actinomycetemcomitans, two prominent periodontopathogens. Bactericidal exposure assays revealed that three of the synthesized NO-releasing polymers were capable of reducing bacterial viability of both species by 99.9% in 2 hr at concentrations of 4 mg ml−1 or lower, reflecting NO's potent and rapid bactericidal action. The NO-releasing CMCs elicited minimal toxicity to human gingival fibroblasts at their bactericidal concentrations following 24-hr exposure.
Supporting Information
| Filename | Description |
|---|---|
| jbma37056-sup-0001-Supinfo.pdfPDF document, 214.8 KB | Appendix S1: Supporting Information. Figure S1: UV–vis absorption spectra of (a) CMC-DETA (solid line) and CMC-DETA/NO (dashed line), (b) CMC-DPTA (solid line) and CMC-DPTA/NO (dashed line), (c) CMC-HEDA (solid line) and CMC-HEDA/NO (dashed line), and (d) CMC-PAPA (solid line) and CMC-PAPA/NO (dashed line), in 50 mM NaOH. |
Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
REFERENCES
- 1Petersen PE, Bourgeois D, Ogawa H, Estupinan-Day S, Ndiaye C. The global burden of oral diseases and risks to oral health. Bull World Health Organ. 2005; 83: 661-669.
- 2Hiroshi O, Petersen PE. The global burden of periodontal disease: Towards integration with chronic disease prevention and control. Periodontol 2000. 2012; 60: 15-39.
- 3Dye BA. Global periodontal disease epidemiology. Periodontol 2000. 2012; 58: 10-25.
- 4Kassebaum NJ, Bernabé E, Dahiya M, Bhandari B, Murray CJL, Marcenes W. Global burden of severe periodontitis in 1990-2010: A systematic review and meta-regression. J Dent Res. 2014; 93: 1045-1053.
- 5Suzuki N, Yoneda M, Hirofuji T. Mixed red-complex bacterial infection in periodontitis. Int J Dent. 2013; 2013: 1-6.
10.1155/2013/587279 Google Scholar
- 6Beck JD, Offenbacher S. Systemic effects of periodontitis: Epidemiology of periodontal disease and cardiovascular disease. J Periodontol. 2005; 76: 2089-2100.
- 7Papapanou PN. Systemic effects of periodontitis: Lessons learned from research on atherosclerotic vascular disease and adverse pregnancy outcomes. Int Dent J. 2015; 65: 283-291.
- 8Deas DE, Moritz AJ, Sagun RS, Gruwell SF, Powell CA. Scaling and root planing vs. conservative surgery in the treatment of chronic periodontitis. Periodontol 2000. 2016; 71: 128-139.
- 9Cobb CM. Microbes, inflammation, scaling and root planing, and the periodontal condition. J Dent Hygeine. 2008; 82: 4-9.
- 10Joshi D, Garg T, Goyal AK, Rath G. Advanced drug delivery approaches against periodontitis. Drug Deliv. 2016; 23: 363-377.
- 11Goodson JM, Offenbacher S, Farr DH, Hogan PE. Periodontal disease treatment by local drug delivery. J Periodontol. 1985; 56: 265-272.
- 12Feres M, Figueiredo LC, Soares GMS, Faveri M. Systemic antibiotics in the treatment of periodontitis. Periodontol. 2015; 67: 131-186.
- 13Gürgan CA, Zaim E, Bakirsoy I, Soykan E. Short-term side effects of 0.2% alcohol-free chlorhexidine mouthrinse used as an adjunct to non-surgical periodontal treatment: A double-blind clinical study. J Periodontol. 2006; 77: 370-384.
- 14Soares GMS, Figueiredo LC, Faveri M, Cortelli SC, Duarte PM, Feres M. Mechanisms of action of systemic antibiotics used in periodontal treatment and mechanisms of bacterial resistance to these drugs. J Appl Oral Sci. 2012; 20: 295-305.
- 15Goodson JM. Gingival crevice fluid flow. Periodontol 2000. 2003; 31: 43-54.
- 16Butler AR, Williams DLH. The physiological role of nitric oxide. Chem Soc Rev. 1993; 22: 233-241.
- 17Carpenter AW, Schoenfisch MH. Nitric oxide release: Part II. Therapeutic applications. Chem Soc Rev. 2012; 41: 3742-3752.
- 18Backlund CJ, Sergesketter AR, Offenbacher S, Schoenfisch MH. Antibacterial efficacy of exogenous nitric oxide on periodontal pathogens. J Dent Res. 2014; 93: 1089-1094.
- 19Backlund CJ, Worley BV, Sergesketter AR, Schoenfisch MH. Kinetic-dependent killing of oral pathogens with nitric oxide. J Dent Res. 2015; 94: 1092-1098.
- 20Privett BJ, Broadnax AD, Bauman SJ, Riccio DA, Schoenfisch MH. Examination of bacterial resistance to exogenous nitric oxide. Nitric Oxide Biol Chem. 2012; 26: 169-173.
- 21Riccio DA, Schoenfisch MH. Nitric oxide release: Part I. Macromolecular scaffolds. Chem Soc Rev. 2012; 41: 3731-3741.
- 22Hrabie JA, Keefer LK. Chemistry of the nitric oxide-releasing diazeniumdiolate (“nitrosohydroxylamine”) functional group and its oxygen-substituted derivatives. Chem Rev. 2002; 102: 1135-1154.
- 23Davies KM, Wink DA, Saavedra JE, Keefer LK. Chemistry of the diazeniumdiolates. 2. Kinetics and mechanism of dissociation to nitric oxide in aqueous solution. J Am Chem Soc. 2001; 123: 5473-5481.
- 24Keefer LK. Fifty years of diazeniumdiolate research. From laboratory curiosity to broad-spectrum biomedical advances. ACS Chem Biol. 2011; 6: 1147-1155.
- 25Francis CV. Sodium Carboxymethylcellulose. Anal Chem. 1953; 25: 941-943.
- 26Kovtun A, Kozlova D, Ganesan K, et al. Chlorhexidine-loaded calcium phosphate nanoparticles for dental maintenance treatment: Combination of mineralising and antibacterial effects. RSC Adv. 2012; 2: 870-875.
- 27Pasqui D, Torricelli P, De Cagna M, Fini M, Barbucci R. Carboxymethyl cellulose - hydroxyapatite hybrid hydrogel as a composite material for bone tissue engineering applications. J Biomed Mater Res A. 2014; 102: 1568-1579.
- 28Teti G, Salvatore V, Focaroli S, et al. In vitro osteogenic and odontogenic differentiation of human dental pulp stem cells seeded on carboxymethyl cellulose-hydroxyapatite hybrid hydrogel. Front Physiol. 2015; 6: 1-10.
- 29Laffleur F. Mucoadhesive polymers for buccal drug delivery. Drug Dev Ind Pharm. 2014; 40: 591-598.
- 30Fonseca-Santos B, Chorilli M. An overview of polymeric dosage forms in buccal drug delivery: State of art, design of formulations and their in vivo performance evaluation. Mater Sci Eng C. 2018; 86: 129-143.
- 31Angela R, Zahir-jouzdani F, Dünnhaupt S, Atyabi F, Bernkop-schnürch A. Mucoadhesive hydrogels for buccal drug delivery: in vitro - in vivo correlation study. Eur J Pharm Biopharm. 2019; 142: 498-505.
- 32Dekina S, Romanovska I, Ovsepyan A, Tkach V, Muratov E. Gelatin/carboxymethyl cellulose mucoadhesive films with lysozyme: Development and characterization. Carbohydr Polym. 2016; 147: 208-215.
- 33Casaburi A, Montoya Rojo Ú, Cerrutti P, Vázquez A, Foresti ML. Carboxymethyl cellulose with tailored degree of substitution obtained from bacterial cellulose. Food Hydrocoll. 2018; 75: 147-156.
- 34Yang L, Wang X, Suchyta DJ, Schoenfisch MH. Antibacterial activity of nitric oxide-releasing hyperbranched polyamidoamines. Bioconjug Chem. 2018; 29: 35-43.
- 35Yang L, Jing L, Jiao Y, et al. In vivo antibacterial efficacy of nitric oxide-releasing hyperbranched polymers against Porphyromonas gingivalis. Mol Pharm. 2019; 16: 4017-4023.
- 36Sutton S. Accuracy of plate counts. J Valid Technol. 2011; 17: 42-46.
- 37Ahonen MJR, Suchyta DJ, Zhu H, Schoenfisch MH. Nitric oxide-releasing alginates. Biomacromolecules. 2018; 19: 1189-1197.
- 38Eggert FM, Drewell L, Bigelow JA, Speck JE, Goldner M. The pH of gingival crevices and periodontal pockets in children, teenagers, and adults. Arch Oral Biol. 1991; 36: 233-238.
- 39Shin JH, Schoenfisch MH. Inorganic/organic hybrid silica nanoparticles as a nitric oxide delivery scaffold. Chem Mater. 2008; 20: 239-249.
- 40Fine DH, Markowitz K, Furgang D, et al. Aggregatibacter actinomycetemcomitans and its relationship to initiation of localized aggressive periodontitis: Longitudinal cohort study of initially healthy adolescents. J Clin Microbiol. 2007; 45: 3859-3869.
- 41Gholizadeh P, Pormohammad A, Eslami H, Shokouhi B, Fakhrzadeh V, Kafil HS. Oral pathogenesis of Aggregatibacter actinomycetemcomitans. Microb Pathog. 2017; 113: 303-311.
- 42Loesche WJ, Gusberti F, Mettraux G, Higgins T, Syed S. Relationship between oxygen tension and subgingival bacterial flora in untreated human periodontal pockets. Infect Immun. 1983; 42: 659-667.
- 43Mettraux GR, Gusberti FA, Graf H. Oxygen tension (pO2) in untreated human periodontal pockets. J Periodontol. 1984; 55: 516-521.
- 44Diaz PI, Rogers AH. The effect of oxygen on the growth and physiology of Porphyromonas gingivalis. Oral Microbiol Immunol. 2004; 19: 88-94.
- 45Chastain-gross RP, Xie G, Bélanger M, et al. Genome sequence of Porphyromonas gingivalis strain A7436. Genome Announc. 2015; 3: 1-2.
10.1128/genomeA.00927-15 Google Scholar
- 46Brunner J, Scheres N, El Idrissi NB, et al. The capsule of Porphyromonas gingivalis reduces the immune response of human gingival fibroblasts. BMC Microbiol. 2010; 10: 1-11.
- 47Singh A, Wyant T, Anaya-bergman C, et al. The capsule of porphyromonas gingivalis leads to a reduction in the host inflammatory response, evasion of phagocytosis, and increase in virulence. Infect Immun. 2011; 79: 4533-4542.
- 48Napoli C, Paolisso G, Casamassimi A, et al. Effects of nitric oxide on cell proliferation: novel insights. J Am Coll Cardiol. 2013; 62: 89-95.
- 49Marchesan J, Girnary MS, Jing L, et al. An experimental murine model to study periodontitis. Nat Protoc. 2018; 13: 2247-2267.
Citing Literature
