Prevention of Murine Influenza a Virus Pneumonitis by Surfactant Nano-Emulsions

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 5×105 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.

[1]  J. Baker,et al.  A novel surfactant nanoemulsion with broad-spectrum sporicidal activity against Bacillus species. , 1999, The Journal of infectious diseases.

[2]  M. Anderson,et al.  Optimization of in situ cellular ELISA performed on influenza A virus-infected monolayers for screening of antiviral agents. , 1999, Journal of virological methods.

[3]  R. Spiro,et al.  Sulphation of N-linked oligosaccharides of vesicular stomatitis and influenza virus envelope glycoproteins: host cell specificity, subcellular localization and identification of substituted saccharides. , 1998, The Biochemical journal.

[4]  I. Schulze Effects of glycosylation on the properties and functions of influenza virus hemagglutinin. , 1997, The Journal of infectious diseases.

[5]  M. Kameswaran,et al.  Olive oil aspiration pneumonia (lipoid) in children , 1997, Tropical medicine & international health : TM & IH.

[6]  E. Saravolac,et al.  Development of a murine hypothermia model for study of respiratory tract influenza virus infection. , 1997, Laboratory animal science.

[7]  W. Reutter,et al.  Antiviral activity of some natural and synthetic sugar analogues , 1991, FEBS letters.

[8]  P. Mills,et al.  Use of telemetry to record body temperature and activity in mice. , 1989, Journal of pharmacological methods.

[9]  J. Cummings,et al.  The Distribution of Doxorubicin in Mice Following Administration in Niosomes , 1988, The Journal of pharmacy and pharmacology.

[10]  G. H. Coombs,et al.  Non‐ionic surfactant vesicles, niosomes, as a delivery system for the anti‐leishmanial drug, sodium stibogluconate , 1986, The Journal of pharmacy and pharmacology.

[11]  A. Florence,et al.  The effect of non‐ionic surfactant vesicle (niosome) entrapment on the absorption and distribution of methotrexate in mice , 1985, The Journal of pharmacy and pharmacology.

[12]  R. Couch,et al.  Effects of Low- and High-Passage Influenza Virus Infection in Normal and Nude Mice , 1977, Infection and immunity.

[13]  G. H. Scott,et al.  Responses of mice immunized with influenza virus by serosol and parenteral routes , 1976, Infection and immunity.

[14]  K. Ikeda OIL ASPIRATION PNEUMONIA (LIPOID PNEUMONIA): CLINICAL, PATHOLOGIC AND EXPERIMENTAL CONSIDERATION , 1935 .

[15]  H. Pinkerton OILS AND FATS: THEIR ENTRANCE INTO AND FATE IN THE LUNGS OF INFANTS AND CHILDREN: A CLINICAL AND PATHOLOGIC REPORT , 1927 .

[16]  R. Sidwell The Mouse Model of Influenza Virus Infection , 1999 .

[17]  H. Schreier,et al.  Povidone-iodine liposomes--an overview. , 1997, Dermatology.

[18]  R. Lamb,et al.  Orthomyxoviridae: The Viruses and Their Replication. , 1996 .

[19]  David R. Cox,et al.  Regression models and life tables (with discussion , 1972 .

[20]  D. Tyrrell,et al.  Studies on the pathogenesis of influenza virus pneumonia in mice. , 1962, The Journal of pathology and bacteriology.