ABSTRACT Burns are one of the most common injuries in both civilian and combat settings and are difficult to treat. This is particularly true when the wounds are infected with antibiotic-resistant bacteria such as methicillin-resistant Staphylococcus aureus (MRSA). A new generation of safe, broadly effective, and easily applied anti-infection agents is needed to successfully prevent and treat infections. Nanoemulsions (NEs) are nanometer-sized particles with a positively charged surfactant at their oil-water interface. In the current study, we further investigated antimicrobial NEs as a treatment to address burn wounds infected by MRSA. Specifically, using a porcine skin model, we infected partial thickness thermal burn wounds with MRSA and then treated it with the nanoemulsion formulation (NB-201) or placebo controls. Bacterial viability after treatment was determined, and inflammation indexes in wounds were scored by histopathology. Topical treatment of infected wounds with NB-201 resulted in reduced colony-forming units (CFUs) compared to placebo treatment. In addition, NB-201 was effective in significantly alleviating inflammation in the treated wounds and promoting wound healing. These results indicate that NB-201 is a promising new agent to treat skin burn wounds infected with MRSA. IMPORTANCE The findings of this study are focused on therapeutic applications of nanotechnology. In the current study, we demonstrated that a nanoemulsion formulation could effectively kill methicillin-resistant Staphylococcus aureus (MRSA) infection in porcine skin burn wounds. Infection of MRSA in burn wound is a common threat to public health and is usually difficult to treat due to limited therapies available. NB-201 was effective in significantly alleviating inflammation in the treated wounds and promoting wound healing. Therefore, the finding of this study has a great potential to make this formulation a novel antimicrobial agent against MRSA.

01 Sep 2010·SurgeryQ2 · MEDICINE

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

Q2 · MEDICINE

Article

Author: Peter A. Ward ; Stewart C. Wang ; Aladdein Mattar ; James R. Baker ; Mark R. Hemmila ; Michael A. Taddonio ; Saman Arbabi ; Tarek Hamouda

BACKGROUNDNanoemulsions 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.METHODSMale 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.RESULTSNB-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.CONCLUSIONTopical 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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Indication	Highest Phase	Country/Location	Organization	Date
Burn infections	Preclinical	-	BlueWillow Biologics	-
Neoplasms	Preclinical	US	NewBiotics, Inc.	-
Wound Infection	Preclinical	-	BlueWillow Biologics	-

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