title: Prevention of murine influenza A virus pneumonitis by surfactant nano-emulsions.
abstract: Non-ionic surfactant nano-emulsions have extensive anti-microbial activity and are biocompatible with skin and mucous membranes at effective concentrations. Two nano-emulsion formulations (8N8 and 20N10) made from soybean oil, tributyl phosphate and Triton X-100, were tested for their ability to prevent murine influenza virus pneumonia in vivo. In the initial study, CD-1 mice were administered various dilutions of the nano-emulsions intranasally, and safe dosages and concentrations were determined. Non-toxic concentrations of the nano-emulsions were then mixed with influenza virus and applied to the nares of mice. Animals receiving mixtures of two different emulsions (8N8 or 20N10) and a LD50 of virus survived the challenge without evidence of viral infection. To determine if the nano-emulsions could prevent influenza virus infection in vivo when used as a prophylactic treatment, the nano-emulsions (8N8 at 1.0% and 20N10 at 1.0% or 0.2%) were applied to mouse nares 90 min before exposure to 5x10(5) p.f.u./ml virus by nebulized aerosol. Animals pretreated with the nano-emulsions had significantly decreased clinical signs of infection. Only 26.0% (8N8 at 1.0%), 31.25% (20N10 at 1.0%) and 37.0% (20N10 at 0.2%) of animals pretreated with nano-emulsion died from pneumonitis, whereas >80.0% of mock pretreated animals succumbed to infection (P<0.005). These findings suggest that non-ionic surfactant nano-emulsions have therapeutic potential for the prevention of influenza virus infection in vivo.
authors.affiliation: Center for Biologic Nanotechnology, Department of Internal Medicine, University of Michigan, Ann Arbor 48109-0648, USA.
authors.forename: B W
authors.initials: BW
authors.lastname: Donovan
authors.forename: J D
authors.initials: JD
authors.lastname: Reuter
authors.forename: Z
authors.initials: Z
authors.lastname: Cao
authors.forename: A
authors.initials: A
authors.lastname: Myc
authors.forename: K J
authors.initials: KJ
authors.lastname: Johnson
authors.forename: J R
authors.initials: JR
authors.lastname: Baker
mesh_terms: D000818:Animals; D000998:Antiviral Agents / Q000627:therapeutic use* / Q000633:toxicity; D004655:Emulsions / Q000627:therapeutic use* / Q000633:toxicity; D005260:Female; D009980:Influenza A virus / Q000187:drug effects*; D008297:Male; D051379:Mice; D011024:Pneumonia, Viral / Q000517:prevention & control*; D013501:Surface-Active Agents / Q000627:therapeutic use* / Q000633:toxicity
chemical_list: D000998:Antiviral Agents; D004655:Emulsions; D013501:Surface-Active Agents