Topical nanoemulsion therapy reduces bacterial wound infection and inflammation after burn injury.
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 x 10(6) 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 10(5) 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]-1beta and IL-6) and the degree of hair follicle cell apoptosis in skin compared to saline-treated controls.


CONCLUSIONS
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.
Hemmila
Mark R
MR
Department of Surgery, University of Michigan Medical School, Ann Arbor, MI 48109-5033, USA. mhemmila@umich.edu
Mattar
Aladdein
A
Taddonio
Michael A
MA
Arbabi
Saman
S
Hamouda
Tarek
T
Ward
Peter A
PA
Wang
Stewart C
SC
Baker
James R
JR
D000818:Animals; D017209:Apoptosis; D001424:Bacterial Infections / Q000201:enzymology / Q000209:etiology / Q000517:prevention & control*; D015415:Biomarkers / Q000378:metabolism; D002056:Burns / Q000150:complications* / Q000209:etiology / Q000473:pathology; D004655:Emulsions / Q000627:therapeutic use*; D006358:Hot Temperature / Q000009:adverse effects; D006801:Humans; D007249:Inflammation / Q000201:enzymology / Q000209:etiology / Q000517:prevention & control*; D053583:Interleukin-1beta / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D008297:Male; D009195:Peroxidase / Q000378:metabolism; D011552:Pseudomonas Infections / Q000201:enzymology / Q000517:prevention & control*; D011550:Pseudomonas aeruginosa; D051381:Rats; D017207:Rats, Sprague-Dawley; D012867:Skin / Q000187:drug effects / Q000473:pathology; D014946:Wound Infection / Q000201:enzymology / Q000209:etiology / Q000517:prevention & control*
D015415:Biomarkers; D004655:Emulsions; D053583:Interleukin-1beta; D015850:Interleukin-6; D009195:Peroxidase