Defense Medical Research and Development
Preclinical Development of an Antimicrobial Nanoemulsion to Investigational New Drug for Multidrug-Resistant Wound Infections
Posted September 20, 2016
Suhe Wang, Ph.D.,
University of Michigan
Burn and wound infections resulting from battlefield injuries account for the majority of combat-related casualties. Delayed treatment or environmental complications experienced on the front lines or attained during evacuation or hospitalization heighten the possibility of wound contamination. These risk factors are compounded by the increasing prevalence of antibiotic-resistant microorganisms that can complicate proper wound healing. There is a recognized critical need for new antibacterial drugs. This need has led to the establishment of the Government’s Task Force for Combating Antibiotic-Resistant Bacteria and a call from national agencies for research to pursue new avenues of antimicrobial treatment.
To address this serious health threat, Principal Investigators Drs. Suhe Wang and John LiPuma, with the support of a Fiscal Year (FY) 2010 Military Infectious Diseases Basic Research Award, formulated nanoemulsions (NEs) composed of varying combinations of cationic and nonionic surfactants and tested them for microbicidal activity. Two lead NE candidates, NB-201and CPC/p407, displayed marked in vitro antimicrobial activity against multi-drug resistant bacterial and fungal strains. Importantly, in pig and mice wound models, NB-201 also demonstrated efficacy against infections with methicillin-resistant Staphylococcus aureus (MRSA), bacteria recognized as a serious health threat in hospital settings.
These promising initial findings led to a recent publication in Military Medicine, wherein Dr. Wang and colleagues demonstrated the efficacy of NEs in vivo using a mouse skin abrasion model. They determined two NEs, NB-201 and NB-402, to be efficacious for S. aureus-infected wounds, reducing bacterial counts by 4-5 and 2-3 log units, respectively. When compared with silver sulfadiazine, the commercially available treatment for S. aureus, NB-201 exhibited comparable efficacy at a more dilute dose, suggesting that this NE may be a viable topical antimicrobial agent.
John LiPuma, M.D.,
University of Michigan
Drs. Wang and LiPuma continued to build upon these promising results and was awarded an FY2014 Military Infectious Diseases Applied Research Award to advance NB-201 closer to the clinic. In pursuit of this goal, the researchers collaborated with Nanobio Corporation to use U.S. Food and Drug Administration (FDA)-mandated current good manufacturing practices (cGMP) in the production of three formulations of NB-201, two of which were found to be stable for at least 9 months in all conditions tested. The PIs found the different NB-201 preparations to be effective in killing an expanded panel of drug-resistant microorganisms that included 10 strains each of Acinetobacter baumanii, MRSA, Pseudomonas aeruginosa, Klebsiella pneumonia, and vancomycin-resistant Enterococcus (VRE) species. They also found NB-201 to be efficacious against several species of fungi in vitro and have confirmed NB-201’s efficacy against MRSA in a pig skin split-thickness wound model. The researchers plan to expand in vitro studies to determine NB-201’s activity against bacterial biofilms, which are notoriously treatment-resistant, and animal studies to determine the in vivo response of VRE, fungi, and polymicrobial infections to NB-201 treatment.
By using cGMP-produced NB-201 in current good laboratory practice (cGLP) toxicity studies and continuing in vitro and in vivo animal model skin and burn wound dose response studies, Drs. Wang and LiPuma hope to acquire enough data to apply for Investigational New Drug status with the FDA, with the goal of testing this promising new therapeutic in humans.
Last updated Tuesday, September 20, 2016