title: Liposome encapsulation of ciprofloxacin improves protection against highly virulent Francisella tularensis strain Schu S4.
abstract: Liposome-encapsulated ciprofloxacin for inhalation (CFI) was investigated as a putative postexposure therapeutic for two strains of Francisella tularensis. The efficacies of oral ciprofloxacin and intranasally instilled CFI could not be distinguished in a mouse model of infection with the F. tularensis live vaccine strain (LVS), where a single dose of either formulation offered full protection against a lethal challenge. However, mouse studies with the more virulent Schu S4 strain of F. tularensis demonstrated that a higher level of protection against a lethal aerosol infection is provided by CFI than by oral ciprofloxacin. In addition, using this infection model, it was possible to discriminate the efficacy of intranasally instilled CFI from that of aerosolized CFI, with aerosolized CFI providing full protection after just a single dose. The improved efficacy of CFI compared to oral ciprofloxacin is likely due to the high sustained concentrations of ciprofloxacin in the lung. In summary, CFI may be a promising therapy, perhaps enabling the prophylactic regimen to be shortened, for use in the event of a deliberate release of F. tularensis. The prophylactic efficacy of CFI against other biological warfare (BW) threat agents also warrants investigation.
authors.affiliation: Department of Biomedical Sciences, Defence Science and Technology Laboratory, Porton Down, Salisbury, Wiltshire, United Kingdom kahamblin@dstl.gov.uk.
authors.forename: Karleigh A
authors.initials: KA
authors.lastname: Hamblin
authors.affiliation: Department of Biomedical Sciences, Defence Science and Technology Laboratory, Porton Down, Salisbury, Wiltshire, United Kingdom.
authors.forename: Stuart J
authors.initials: SJ
authors.lastname: Armstrong
authors.affiliation: Department of Biomedical Sciences, Defence Science and Technology Laboratory, Porton Down, Salisbury, Wiltshire, United Kingdom.
authors.forename: Kay B
authors.initials: KB
authors.lastname: Barnes
authors.affiliation: Department of Biomedical Sciences, Defence Science and Technology Laboratory, Porton Down, Salisbury, Wiltshire, United Kingdom.
authors.forename: Carwyn
authors.initials: C
authors.lastname: Davies
authors.affiliation: Defence Research and Development Canada, Suffield Research Center, Ralston, Alberta, Canada.
authors.forename: Jonathan P
authors.initials: JP
authors.lastname: Wong
authors.affiliation: Aradigm Corporation, Hayward, California, USA.
authors.forename: James D
authors.initials: JD
authors.lastname: Blanchard
authors.affiliation: Department of Biomedical Sciences, Defence Science and Technology Laboratory, Porton Down, Salisbury, Wiltshire, United Kingdom.
authors.forename: Sarah V
authors.initials: SV
authors.lastname: Harding
authors.affiliation: Department of Biomedical Sciences, Defence Science and Technology Laboratory, Porton Down, Salisbury, Wiltshire, United Kingdom.
authors.forename: Andrew J H
authors.initials: AJ
authors.lastname: Simpson
authors.affiliation: Department of Biomedical Sciences, Defence Science and Technology Laboratory, Porton Down, Salisbury, Wiltshire, United Kingdom.
authors.forename: Helen S
authors.initials: HS
authors.lastname: Atkins
mesh_terms: D000280:Administration, Inhalation; D000281:Administration, Intranasal; D000336:Aerosols; D000818:Animals; D001428:Bacterial Vaccines / Q000276:immunology; D001682:Biological Availability; D002939:Ciprofloxacin / Q000008:administration & dosage* / Q000493:pharmacokinetics; D004195:Disease Models, Animal; D005260:Female; D005604:Francisella tularensis / Q000187:drug effects* / Q000276:immunology / Q000472:pathogenicity; D008081:Liposomes; D008168:Lung / Q000276:immunology / Q000382:microbiology; D051379:Mice; D008807:Mice, Inbred BALB C; D016019:Survival Analysis; D014406:Tularemia / Q000188:drug therapy*; D014613:Vaccines, Attenuated / Q000276:immunology*; D014774:Virulence
chemical_list: D000336:Aerosols; D001428:Bacterial Vaccines; D008081:Liposomes; D014613:Vaccines, Attenuated; D002939:Ciprofloxacin