Surgery
Volume 148, Issue 3 , Pages 499-509, September 2010

Topical nanoemulsion therapy reduces bacterial wound infection and inflammation after burn injury

  • Mark R. Hemmila, MD

      Affiliations

    • Department of Surgery, University of Michigan Medical School, Ann Arbor, MI
    • Corresponding Author InformationReprint requests: Mark R. Hemmila, MD, Trauma Burn Center, University of Michigan Health System, 1B407 University Hospital, 1500 E. Medical Center Drive, SPC 5033, Ann Arbor, MI 48109-5033.
    • ,
  • Aladdein Mattar, MD

      Affiliations

    • Department of Surgery, University of Michigan Medical School, Ann Arbor, MI
    • ,
  • Michael A. Taddonio, BS

      Affiliations

    • Department of Surgery, University of Michigan Medical School, Ann Arbor, MI
    • ,
  • Saman Arbabi, MD

      Affiliations

    • Department of Surgery, University of Washington Medical School, Seattle, WA
    • ,
  • Tarek Hamouda, MD, PhD

      Affiliations

    • NanoBio Corporation, Ann Arbor, MI
    • ,
  • Peter A. Ward, MD

      Affiliations

    • Department of Pathology, University of Michigan Medical School, Ann Arbor, MI
    • ,
  • Stewart C. Wang, MD, PhD

      Affiliations

    • Department of Surgery, University of Michigan Medical School, Ann Arbor, MI
    • ,
  • James R. Baker Jr., MD

      Affiliations

    • Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, MI
    • NanoBio Corporation, Ann Arbor, MI

Accepted 8 January 2010. published online 02 March 2010.

Background

Nanoemulsions are broadly antimicrobial oil-in-water emulsions containing nanometer-sized droplets stabilized with surfactants. We hypothesize that topical application of a nanoemulsion compound (NB-201) can attenuate burn wound infection. In addition to reducing infection, nanoemulsion therapy may modulate dermal inflammatory signaling and thereby lessen inflammation following thermal injury.

Methods

Male Sprague-Dawley rats underwent a 20% total body surface area scald burn to create a partial-thickness burn injury. Animals were resuscitated with Ringer's lactate solution and the wound covered with an occlusive dressing. At 8 hours after injury, the burn wound was inoculated with 1 × 106 colony-forming units (CFUs) of Pseudomonas aeruginosa. NB-201, NB-201 placebo, 5% mafenide acetate solution, or 0.9% saline (control) was applied onto the wound at 16 and 24 hours after burn injury. Skin was harvested 32 hours postburn for quantitative wound culture and determination of inflammatory mediators in tissue homogenates.

Results

NB-201 decreased mean bacterial growth in the burn wound by 1,000-fold, with only 13% (3/23) of animals having P. aeruginosa counts greater than 105 CFU/g tissue versus 91% (29/32) in the control group (P < .0001). Treatment with NB-201 attenuated neutrophil sequestration in the treatment group as measured by myeloperoxidase assay and by histology. It also significantly decreased levels of proinflammatory cytokines (interleukin [IL]-1β and IL-6) and the degree of hair follicle cell apoptosis in skin compared to saline-treated controls.

Conclusion

Topical NB-201 substantially decreased bacterial growth in a partial-thickness burn model. This decrease in the level of wound infection was associated with an attenuation of the local dermal inflammatory response and diminished neutrophil sequestration. NB-201 represents a novel potent antimicrobial and anti-inflammatory treatment for use in burn wounds.

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 Supported in part by research grants from the National Institutes of Health (K08-GM078610 to M.R.H.) and joint support from the American College of Surgeons and the American Association for the Surgery of Trauma (to M.R.H.)

 James R. Baker Jr, MD, is the Executive Chairman and Chief Executive Officer of NanoBio Corporation, Ann Arbor, MI; Tarek Hamouda, MD, PhD, is the Director of Vaccine Research for NanoBio Corporation, Ann Arbor, MI.

PII: S0039-6060(10)00007-3

doi:10.1016/j.surg.2010.01.001

Surgery
Volume 148, Issue 3 , Pages 499-509, September 2010

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