Screening of Nanoemulsion Formulations and Identification of NB-201 as an Effective Topical Antimicrobial for Staphylococcus aureus in a Mouse Model of Infected Wounds

Mil Med. 2016 May;181(5 Suppl):259-64. doi: 10.7205/MILMED-D-15-00186.

Abstract

Despite advances in antimicrobial therapies, wound infection remains a global public health concern. We aimed to formulate and assess various nanoemulsions (NEs) for potential effectiveness as stable antimicrobial agents suitable for topic application. A total of 106 NEs were developed that varied with respect to nonionic and cationic surfactants. Stability testing demonstrated that the NEs tested are broadly stable, with 97/106 formulations passing 2-week stability tests. Two NEs, NB-201 and NB-402, were selected to test antimicrobial activity in a wound model in mice. Skin abrasion wounds were infected with Staphylococcus aureus followed by NE treatment. Infected skin was then evaluated by measuring colony forming units. NB-201 reduced median bacterial counts by 4 to 5 log compared to animals treated with saline, whereas NB-402 reduced bacterial counts by 2 to 3 log. Additional stability tests on NB-201 demonstrated that NB-201 is stable in the presence of human serum, and is stable for at least 6 months at 5°C, 25°C, and 40°C. Finally, in in vitro studies, NB-201 was found to be effective against S. aureus at a higher dilution than the commercially available silver sulfadiazine. Altogether these results demonstrate that NB-201 is a stable and effective topical antimicrobial for the treatment of S. aureus.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Anti-Infective Agents, Local / administration & dosage
  • Anti-Infective Agents, Local / pharmacology
  • Anti-Infective Agents, Local / therapeutic use
  • Benzalkonium Compounds / administration & dosage
  • Benzalkonium Compounds / pharmacology*
  • Benzalkonium Compounds / therapeutic use
  • Cetylpyridinium / administration & dosage
  • Cetylpyridinium / pharmacology*
  • Cetylpyridinium / therapeutic use
  • Drug Combinations
  • Mice
  • Models, Animal
  • Poloxamer / administration & dosage
  • Poloxamer / pharmacology*
  • Poloxamer / therapeutic use
  • Polysorbates / administration & dosage
  • Polysorbates / pharmacology*
  • Polysorbates / therapeutic use
  • Silver Sulfadiazine / administration & dosage
  • Silver Sulfadiazine / pharmacology
  • Silver Sulfadiazine / therapeutic use
  • Soybean Oil / administration & dosage
  • Soybean Oil / pharmacology*
  • Soybean Oil / therapeutic use
  • Staphylococcal Infections / drug therapy*
  • Staphylococcus aureus / drug effects*
  • Wound Infection / drug therapy
  • Wound Infection / prevention & control

Substances

  • Anti-Infective Agents, Local
  • Benzalkonium Compounds
  • Drug Combinations
  • NB-201 nanoemulsion
  • NB-402 nanoemulsion
  • Polysorbates
  • Poloxamer
  • Soybean Oil
  • Cetylpyridinium
  • Silver Sulfadiazine