1887

Abstract

Topical delivery of nitric oxide (NO) through a wound dressing has the potential to reduce wound infections and improve healing of acute and chronic wounds. This study characterized the antibacterial efficacy of an ointment containing NO-loaded, zinc-exchanged zeolite A that releases NO upon contact with water. The release rate of NO from the ointment was measured using a chemiluminescence detection system. Minimum bactericidal concentration assays were performed using five common wound pathogens, including Gram-negative bacteria ( and ), Gram-positive bacteria ( and meticillin-resistant ) and a fungus (). The time dependence of antimicrobial activity was characterized by performing log-reduction assays at four time points after 1–8 h ointment exposure. The cytotoxicity of the ointment after 24 h was assessed using cultured 3T3 fibroblast cells. Minimum microbicidal concentrations (MMCs) for bacterial organisms (5×10 c.f.u.) ranged from 50 to 100 mg ointment (ml media); the MMC for (5×10 c.f.u.) was 50 mg ointment (ml media). Five to eight log reductions in bacterial viability and three log reductions in fungal viability were observed after 8 h exposure to NO–zeolite ointment compared with untreated organisms. Fibroblasts remained viable after 24 h exposure to the same concentration of NO–zeolite ointment as was used in antimicrobial tests. In parallel studies, full-thickness cutaneous wounds on Zucker obese rats healed faster than wounds treated with a control ointment. These data indicate that ointment containing NO-loaded zeolites could potentially be used as a broad-spectrum antimicrobial wound-healing dressing.

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2014-02-01
2024-04-26
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References

  1. Balin A. K., Pratt L. 2002; Dilute povidone-iodine solutions inhibit human skin fibroblast growth. Dermatol Surg 28:210–214 [View Article][PubMed]
    [Google Scholar]
  2. Burd A., Kwok C. H., Hung S. C., Chan H. S., Gu H., Lam W. K., Huang L. 2007; A comparative study of the cytotoxicity of silver-based dressings in monolayer cell, tissue explant, and animal models. Wound Repair Regen 15:94–104 [View Article][PubMed]
    [Google Scholar]
  3. Eardley W. G., Watts S. A., Clasper J. C. 2012; Limb wounding and antisepsis: iodine and chlorhexidine in the early management of extremity injury. Int J Low Extrem Wounds 11:213–223 [View Article][PubMed]
    [Google Scholar]
  4. Fox S., Wilkinson T. S., Wheatley P. S., Xiao B., Morris R. E., Sutherland A., Simpson A. J., Barlow P. G., Butler A. R., Megson I. L. 2010; NO-loaded Zn2+-exchanged zeolite materials: a potential bifunctional anti-bacterial strategy. Acta Biomater 6:1515–1521 [View Article][PubMed]
    [Google Scholar]
  5. Friedman A. J., Han G., Navati M. S., Chacko M., Gunther L., Alfieri A., Friedman J. M. 2008; Sustained release nitric oxide releasing nanoparticles: characterization of a novel delivery platform based on nitrite containing hydrogel/glass composites. Nitric Oxide 19:12–20 [View Article][PubMed]
    [Google Scholar]
  6. Ghaffari A., Miller C. C., McMullin B., Ghahary A. 2006; Potential application of gaseous nitric oxide as a topical antimicrobial agent. Nitric Oxide 14:21–29 [View Article][PubMed]
    [Google Scholar]
  7. Ghaffari A., Jalili R., Ghaffari M., Miller C., Ghahary A. 2007; Efficacy of gaseous nitric oxide in the treatment of skin and soft tissue infections. Wound Repair Regen 15:368–377 [View Article][PubMed]
    [Google Scholar]
  8. Jones M. L., Ganopolsky J. G., Labbé A., Wahl C., Prakash S. 2010; Antimicrobial properties of nitric oxide and its application in antimicrobial formulations and medical devices. Appl Microbiol Biotechnol 88:401–407 [View Article][PubMed]
    [Google Scholar]
  9. Keefer L. K. 2005; Nitric oxide (NO)- and nitroxyl (HNO)-generating diazeniumdiolates (NONOates): emerging commercial opportunities. Curr Top Med Chem 5:625–636 [View Article][PubMed]
    [Google Scholar]
  10. Kröncke K. D., Suschek C. V. 2008; Adulterated effects of nitric oxide-generating donors. J Invest Dermatol 128:258–260 [View Article][PubMed]
    [Google Scholar]
  11. Li Y., Lee P. I. 2010; Controlled nitric oxide delivery platform based on S-nitrosothiol conjugated interpolymer complexes for diabetic wound healing. Mol Pharm 7:254–266 [View Article][PubMed]
    [Google Scholar]
  12. Liu H. A., Balkus K. J. Jr 2009; Novel delivery system for the bioregulatory agent nitric oxide. Chem Mater 21:5032–5041 [View Article]
    [Google Scholar]
  13. Miller C. C., Miller M. K., Ghaffari A., Kunimoto B. 2004; Treatment of chronic nonhealing leg ulceration with gaseous nitric oxide: a case study. J Cutan Med Surg 8:233–238 [View Article][PubMed]
    [Google Scholar]
  14. Morris R. E., Wheatley P. S. 2008; Gas storage in nanoporous materials. Angew Chem Int Ed Engl 47:4966–4981 [View Article][PubMed]
    [Google Scholar]
  15. Mowbray M., Tan X., Wheatley P. S., Rossi A. G., Morris R. E., Weller R. B. 2008; Topically applied nitric oxide induces T-lymphocyte infiltration in human skin, but minimal inflammation. J Invest Dermatol 128:352–360 [View Article][PubMed]
    [Google Scholar]
  16. Ormerod A. D., Copeland P., Hay I., Husain A., Ewen S. W. 1999; The inflammatory and cytotoxic effects of a nitric oxide releasing cream on normal skin. J Invest Dermatol 113:392–397 [View Article][PubMed]
    [Google Scholar]
  17. Rizk M., Witte M. B., Barbul A. 2004; Nitric oxide and wound healing. World J Surg 28:301–306 [View Article][PubMed]
    [Google Scholar]
  18. Shin J. H., Metzger S. K., Schoenfisch M. H. 2007; Synthesis of nitric oxide-releasing silica nanoparticles. J Am Chem Soc 129:4612–4619 [View Article][PubMed]
    [Google Scholar]
  19. Steed D. L. 2003; Wound-healing trajectories. Surg Clin North Am 83:547–555, vi–vii [View Article][PubMed]
    [Google Scholar]
  20. Thomas D. D., Liu X., Kantrow S. P., Lancaster J. R. Jr 2001; The biological lifetime of nitric oxide: implications for the perivascular dynamics of NO and O2. Proc Natl Acad Sci U S A 98:355–360 [View Article][PubMed]
    [Google Scholar]
  21. Vermeulen H., Westerbos S. J., Ubbink D. T. 2010; Benefit and harm of iodine in wound care: a systematic review. J Hosp Infect 76:191–199 [View Article][PubMed]
    [Google Scholar]
  22. Weller R., Finnen M. J. 2006; The effects of topical treatment with acidified nitrite on wound healing in normal and diabetic mice. Nitric Oxide 15:395–399 [View Article][PubMed]
    [Google Scholar]
  23. Wheatley P. S., Butler A. R., Crane M. S., Fox S., Xiao B., Rossi A. G., Megson I. L., Morris R. E. 2006; NO-releasing zeolites and their antithrombotic properties. J Am Chem Soc 128:502–509 [View Article][PubMed]
    [Google Scholar]
  24. Wheatley P. S., McKinlay A. C., Morris R. E. 2008; A comparison of zeolites and metal organic frameworks as storage and delivery vehicles for biologically active nitric oxide. In: Zeolites and related materials: trends, targets and challenges, Proceedings of the 4th International FEZA Conference, Paris, France, 2–6 September 2008.Edited by Gédéon A., Massiani P., Babonneau F. Stud. Surface Sci Catalysis 174441–446 [View Article][PubMed]
    [Google Scholar]
  25. Zacharia I. G., Deen W. M. 2005; Diffusivity and solubility of nitric oxide in water and saline. Ann Biomed Eng 33:214–222 [View Article][PubMed]
    [Google Scholar]
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