title: Nanoemulsion Therapy for Burn Wounds Is Effective as a Topical Antimicrobial Against Gram-Negative and Gram-Positive Bacteria.
abstract: The aim of this study is to investigate the antimicrobial efficacy of two different nanoemulsion (NE) formulations against Gram-positive and Gram-negative bacteria in an in vivo rodent scald burn model. Male Sprague-Dawley rats were anesthetized and received a partial-thickness scald burn. Eight hours after burn injury, the wound was inoculated with 1 × 10(8) colony-forming units of Pseudomonas aeruginosa or Staphylococcus aureus. Treatment groups consisted of two different NE formulations (NB-201 and NB-402), NE vehicle, or saline. Topical application of the treatment was performed at 16 and 24 hours after burn injury. Animals were killed 32 hours after burn injury, and skin samples were obtained for quantitative wound culture and determination of dermal inflammation markers. In a separate set of experiments, burn wound progression was measured histologically after 72 hours of treatment. Both NE formulations (NB-201 and NB-402) significantly reduced burn wound infections with either P. aeruginosa or S. aureus and decreased median bacterial counts at least three logs when compared with animals with saline applications (p < .0001). NB-201 and NB-402 also decreased dermal neutrophil recruitment and sequestration into the wound as measured by myeloperoxidase (MPO) assay and histopathology (p < .05). In addition, there was a decrease in the proinflammatory dermal cytokines (interleukin 1-beta [IL-1β], IL-6, and tumor necrosis factor alpha [TNF-α]) and the neutrophil chemoattractants CXCL1 and CXCL2. Using histologic examination, it was found that both NB-201 and NB-402 appeared to suppress burn wound progression 72 hours after injury. Topically applied NB-201 and NB-402 are effective in decreasing Gram-positive and Gram-negative bacteria growth in burn wounds, reducing inflammation, and abrogating burn wound progression.
authors.affiliation: From the *Department of Surgery, The University of Michigan, Ann Arbor; †NanoBio Corporation, Ann Arbor, Michigan; ‡Unit for Laboratory Animal Medicine, The University of Michigan, Ann Arbor; and §Michigan Nanotechnology Institute for Medicine and Biological Sciences, The University of Michigan, Ann Arbor.
authors.forename: Vladislav A
authors.initials: VA
authors.lastname: Dolgachev
authors.forename: Susan M
authors.initials: SM
authors.lastname: Ciotti
authors.forename: Rone
authors.initials: R
authors.lastname: Eisma
authors.forename: Stephen
authors.initials: S
authors.lastname: Gracon
authors.forename: J Erby
authors.initials: JE
authors.lastname: Wilkinson
authors.forename: James R
authors.initials: JR
authors.lastname: Baker
authors.forename: Mark R
authors.initials: MR
authors.lastname: Hemmila
mesh_terms: D000818:Animals; D001548:Benzalkonium Compounds / Q000494:pharmacology*; D015415:Biomarkers / Q000378:metabolism; D002056:Burns / Q000382:microbiology*; D002594:Cetylpyridinium / Q000494:pharmacology*; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D004338:Drug Combinations; D004655:Emulsions / Q000494:pharmacology*; D006090:Gram-Negative Bacteria / Q000187:drug effects; D006094:Gram-Positive Bacteria / Q000187:drug effects; D008297:Male; D020556:Neutrophil Infiltration; D020442:Poloxamer / Q000494:pharmacology*; D011136:Polysorbates / Q000494:pharmacology*; D011552:Pseudomonas Infections / Q000188:drug therapy* / Q000382:microbiology*; D011550:Pseudomonas aeruginosa / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D013024:Soybean Oil / Q000494:pharmacology*; D013203:Staphylococcal Infections / Q000188:drug therapy* / Q000382:microbiology*; D013211:Staphylococcus aureus / Q000187:drug effects; D014946:Wound Infection / Q000188:drug therapy* / Q000382:microbiology*
chemical_list: D001548:Benzalkonium Compounds; D015415:Biomarkers; D016207:Cytokines; D004338:Drug Combinations; D004655:Emulsions; C000612847:NB-201 nanoemulsion; C000612848:NB-402 nanoemulsion; D011136:Polysorbates; D020442:Poloxamer; D013024:Soybean Oil; D002594:Cetylpyridinium