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Wound Decontamination

October 12, 2010  Media contact: Anne Rueter
E-mail: arueter@umich.edu

Grant to test nanotech anti-infective agent for soldiers' wounds

$1.5 million DOD award allows U-M scientists to pursue new application for nanoemulsion technology.

Grant to test nanotech anti-infective agent for soldiers' wounds

ANN ARBOR, Mich. — The U.S. Department of Defense has awarded $1.5 million over three years to the Michigan Nanotechnology Institute for Medicine and Biological Sciences and to Ann Arbor-based NanoBio Corporation to develop and test nanoemulsions with potential to fight a wide range of wound infections, including drug-resistant forms.


Soldiers in Iraq and Afghanistan get infections, sometimes life-threatening, from shrapnel wounds, IED blast injuries and burns.  Bacteria from soil, air and a soldier’s skin can enter wounds on the battlefield.  A treatment easily applied in battle zones and in hospitals that is broadly effective against bacteria, viruses and fungi would help reduce these infections.

Present therapies aren’t effective enough against antibiotic-resistant

strains of bacteria, and don’t prevent or control a problem soldiers with severe burns encounter: They may fall victim to long-lasting inflammatory responses that delay healing.

 

ANN ARBOR, Mich. — The U.S. Department of Defense has awarded $1.5 million over three years to the Michigan Nanotechnology Institute for Medicine and Biological Sciences and to Ann Arbor-based NanoBio Corporation to develop and test nanoemulsions with potential to fight a wide range of wound infections, including drug-resistant forms.


Soldiers in Iraq and Afghanistan get infections, sometimes life-threatening, from shrapnel wounds, IED blast injuries and burns.  Bacteria from soil, air and a soldier’s skin can enter wounds on the battlefield.  A treatment easily applied in battle zones and in hospitals that is broadly effective against bacteria, viruses and fungi would help reduce these infections.


Present therapies aren’t effective enough against antibiotic-resistant strains of bacteria, and don’t prevent or control a problem soldiers with severe burns encounter: They may fall victim to long-lasting inflammatory responses that delay healing.
 

“A broadly effective nanoemulsion-based wound treatment that can be safely and easily applied at the time of injury, without causing pain or interfering with wound healing, would have great value to prevent infection, increase survival and enable more rapid healing of wounded United States military personnel,” says James R. Baker Jr., M.D., the principal investigator for the grant.

 
Baker directs the Michigan Nanotechnology Institute for Medicine and Biological Sciences (MNIMBS) at U-M. He is the Ruth Dow Doan Professor of Nanotechnology and allergy division chief at the U-M Medical School and is founder and CEO of NanoBio Corporation.

Nanoemulsions are made of soybean oil, alcohol, water and surfactants emulsified into droplets 200 to 600 nanometers in diameter. They have proved effective at killing a variety of bacteria, fungi and viruses in previous research.


The U-M Nanotechnology Institute and NanoBio will use the grant to develop 10 new formulations of nanoemulsions against bacteria, fungi and spores in lab culture studies, followed by animal studies for effectiveness and safety. If successful, the resulting nanoemulsion treatment would proceed to human trials. 


The grant allows U-M and NanoBio scientists to investigate another promising application for nanoemulsion technology developed by Baker with Department of Defense funds in the 1990s. Uses for nanoemulsions include treatments for cold sores, now in phase 3 clinical trials, and for toenail fungus and cystic fibrosis infections, as well as vaccines against influenza and bioterrorism agents.


In a study published earlier this year (see abstract in Surgery below),  U-M researchers found that a nanoemulsion lotion used to treat burns in animals was able to reduce bacterial growth one-thousand-fold compared to control animals receiving no treatment or a placebo. The nanoemulsion also reduced inflammation processes that can cause burn injuries to worsen.


Patents/Disclosures: The patented nanoemulsion technology is licensed by U-M to NanoBio Corporation. Baker holds an equity interest in the company.


Co- investigators for the project: John LiPuma, M.D., professor of pediatrics and communicable diseases, U-M Medical School; Mark Hemmila, M.D., associate professor of surgery, U-M Medical School and the U-MTrauma Burn Research Laboratory; Douglas Smith, Ph.D., research assistant professor, U-M Department of Internal Medicine and MNIMBS; Paul E. Makidon, Ph.D., D.V.M., research investigator, U-M Department of Internal Medicine, Unit for Laboratory Animal Medicine and MNIMBS; Susan Ciotti, Ph.D., director of formulations research and development, NanoBio Corporation.

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Surgery. 2010 Sep;148(3):499-509. Epub 2010 Mar 2.

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

Hemmila MR, Mattar A, Taddonio MA, Arbabi S, Hamouda T, Ward PA, Wang SC, Baker JR Jr.

Department of Surgery, University of Michigan Medical School, Ann Arbor, MI 48109-5033, USA. mhemmila@umich.edu

Abstract

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.

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.

Copyright 2010 Mosby, Inc. All rights reserved.

PMID: 20189619 [PubMed - indexed for MEDLINE]PMCID: PMC2891388 [Available on 2011/9/1]

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