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Hamouda et al., Sporicidal Activity of BCTP Nanoemulsion Page 10 of 12 past 1: 100, higher concentrations of the emulsions (1 : 10) were used for the in vivo studies to make sure they remained effective after dilution with body fluids. Other experiments show that testing BCTP 401 in mice under similar conditions demonstrated similar effects. These results suggest that decontamination of spores prior to or after exposure can effectively reduce the morbidity and mortality from B. cereus infection. This appeared to be a valuable application, because unlike other sporicidal agents, BCTP or BCTP 401 did not demonstrate any toxic effects, grossly or by histopathologic examination of the mice [26]. Other tests in mice showed that these emulsions are nontoxic if administered intramuscularly, intranasally, or orally, providing other potential sites for treatment. BCTP and its derivative BCTP 401 appear to have great potential as environmental decontamination — agents or for treatment of exposed persons in either a military operation or a terrorist attack. The inactivation of a broad range of pathogens, including vegetative bacteria, enveloped viruses [27] (unpublished data), and bacterial spores, combined with low toxicity in experimental animals, seems to make it suitable for use as a general decontamination agent that can be deployed even before a specific pathogen is identified. The nanoemulsions can be rapidly produced in large quantities and are stable for many months unless frozen, which causes separation of the oil and lipid phases. Undiluted, they have the texture of a semisolid cream and can be applied topically by hand or mixed with water. Diluted, they have a consistency and appearance similar to skim milk and can be sprayed to decontaminate surfaces or potentially interact with aerosolized spores before inhalation. These properties provide a flexibility that will be useful for a broad range of decontamination applications. Further studies are warranted to determine the exact mechanism of the sporicidal effect of BCTP and its derivatives, and this may lead to further improvement in formulations. Acknowledgments We thank Shaun B. Jones, Jane Alexander, and Lawrence DuBoise (Defense Science Office, Defense Advanced Research Project Agency) for their support; Bruce Ivins, Patricia Fellows, Mara Linscott, Arthur Friedlander, and the staff of USAMRIDD for their technical support and helpful suggestions in the performance of the initial anthrax studies; Martin Hugh-Jones, Kimothy Smith, and Pamala Coker for supplying the characterized B. anthracis strains and the space at Louisiana State University (Baton Rouge); Robin Kunkel (Department of Pathology, University of Michigan) for her help with electron microscopy preparations; and G. Morris and A. Shih for their technical assistance with manuscript preparation. References 1. Dragon DC, Rennie RP. The ecology of anthrax spores: tough but not invincible. Can Vet J 1995; 36:295—-301. First citation in article | PubMed 2. Welkos SL, Keener TJ, Gibbs PH. Differences in susceptibility of inbred mice to Bacillus anthracis. Infect Immun 1986; 51:795-800. First citation in article | PubMed 3. Franz DR, Jahrling PB, Friedlander AM, et al. Clinical recognition and management of patients exposed to biological warfare agents. JAMA 1997; 278:399-411. First citation in article | PubMed 4. Pile JC, Malone JD, Eitzen EM, Friedlander AM. Anthrax as a potential biological weapon. Arch Intern Med 1998; 158:429-34. First citation in article | PubMed http://www journals.uchicago.edu/JID/j ournal/issues/v180n6/990281/990281 text.html 2/18/2005