title: Inhaled Liposomal Ciprofloxacin Protects against a Lethal Infection in a Murine Model of Pneumonic Plague.
abstract: Inhalation ofYersinia pestiscan lead to pneumonic plague, which without treatment is inevitably fatal. Two novel formulations of liposome-encapsulated ciprofloxacin, 'ciprofloxacin for inhalation' (CFI, Lipoquin®) and 'dual release ciprofloxacin for inhalation' (DRCFI, Pulmaquin®) containing CFI and ciprofloxacin solution, are in development. These were evaluated as potential therapies for infection withY. pestis. In a murine model of pneumonic plague, human-like doses of aerosolized CFI, aerosolized DRCFI or intraperitoneal (i.p.) ciprofloxacin were administered at 24 h (representing prophylaxis) or 42 h (representing treatment) post-challenge. All three therapies provided a high level of protection when administered 24 h post-challenge. A single dose of CFI, but not DRCFI, significantly improved survival compared to a single dose of ciprofloxacin. Furthermore, single doses of CFI and DRCFI reduced bacterial burden in lungs and spleens to below the detectable limit at 60 h post-challenge. When therapy was delayed until 42 h post-challenge, a single dose of CFI or DRCFI offered minimal protection. However, single doses of CFI or DRCFI were able to significantly reduce the bacterial burden in the spleen compared to empty liposomes. A three-day treatment regimen of ciprofloxacin, CFI, or DRCFI resulted in high levels of protection (90-100% survival). This study suggests that CFI and DRCFI may be useful therapies forY. pestisinfection, both as prophylaxis and for the treatment of plague.
authors.affiliation: CBR Division, Defence Science and Technology Laboratory, Porton Down Salisbury, UK.
authors.forename: Karleigh A
authors.initials: KA
authors.lastname: Hamblin
authors.affiliation: CBR Division, Defence Science and Technology Laboratory, Porton Down Salisbury, UK.
authors.forename: Stuart J
authors.initials: SJ
authors.lastname: Armstrong
authors.affiliation: CBR Division, Defence Science and Technology Laboratory, Porton Down Salisbury, UK.
authors.forename: Kay B
authors.initials: KB
authors.lastname: Barnes
authors.affiliation: CBR Division, Defence Science and Technology Laboratory, Porton Down Salisbury, UK.
authors.forename: Carwyn
authors.initials: C
authors.lastname: Davies
authors.affiliation: CBR Division, Defence Science and Technology Laboratory, Porton Down Salisbury, UK.
authors.forename: Thomas
authors.initials: T
authors.lastname: Laws
authors.affiliation: Aradigm Corporation, Hayward CA, USA.
authors.forename: James D
authors.initials: JD
authors.lastname: Blanchard
authors.affiliation: Aradigm Corporation, Hayward CA, USA.
authors.forename: Sarah V
authors.initials: SV
authors.lastname: Harding
authors.affiliation: CBR Division, Defence Science and Technology Laboratory, Porton DownSalisbury, UK; Biosciences, University of ExeterExeter, UK.
authors.forename: Helen S
authors.initials: HS
authors.lastname: Atkins
keywords: Plague; Yersinia pestis; biological warfare agents; ciprofloxacin; inhalation exposure; liposomal drug delivery