title: Nanoaerosols reduce required effective dose of liposomal levofloxacin against pulmonary murine Francisella tularensis subsp. novicida infection.
abstract: BACKGROUND
  The Institute of Theoretical and Experimental Biophysics in Moscow recently developed a new nanoaerosol generator. This study evaluated this novel technology, which has the potential to enhance therapeutic delivery, with the goal of using the generator to treat pulmonary Francisella tularensis subsp. novicida (F. novicida) infections in BALB/c mice.
  
  
  RESULTS
  First, the analysis of quantum dots distribution in cryosections of murine lungs demonstrated that nanoaerosols penetrate the alveoli and spread more homogenously in the lungs than upon intranasal delivery. Second, the generator was used to aerosolize the antibiotic levofloxacin to determine the effectiveness of nanoaerosolized levofloxacin as treatment against F. novicida. The generator was capable of delivering a sufficient dose of nanoaerosolized liposome-encapsulated levofloxacin to rescue mice against 100LD50 of F. novicida.
  
  
  CONCLUSIONS
  The nanoaerosol-delivered dosage of liposome-encapsulated levofloxacin required to rescue mice is approximately 94× lower than the oral required dose and approximately 8× lower than the intraperitoneal dose required for rescue. In addition, treatment with nanoaerosols consumes less total volume of therapeutic solutions and is gentler on sprayed material than the aerosolization by a conventional three-jet Collison nebulizer as seen by the preservation of liposomes. This could represent a significant advance for the use of expensive therapeutics and lung directed therapies.
authors.affiliation: School of Systems Biology and National Center for Biodefense and Infectious Diseases, George Mason University, MS1H8, Manassas, VA, 20110, USA.
authors.forename: Crystal N
authors.initials: CN
authors.lastname: Propst
authors.affiliation: School of Systems Biology and National Center for Biodefense and Infectious Diseases, George Mason University, MS1H8, Manassas, VA, 20110, USA.
authors.forename: Albert O
authors.initials: AO
authors.lastname: Nwabueze
authors.affiliation: Institute of Theoretical and Experimental Biophysics of the Russian Academy of Sciences, Pushchino, Moscow Region, 142290, Russia.
authors.forename: Igor L
authors.initials: IL
authors.lastname: Kanev
authors.affiliation: School of Systems Biology and National Center for Biodefense and Infectious Diseases, George Mason University, MS1H8, Manassas, VA, 20110, USA.
authors.forename: Rachel E
authors.initials: RE
authors.lastname: Pepin
authors.affiliation: CBR Concepts and Experimentation Branch (Z21), Dahlgren Division, Naval Surface Warfare Center, Dahlgren, VA, 22448, USA.
authors.forename: Bradford W
authors.initials: BW
authors.lastname: Gutting
authors.affiliation: School of Systems Biology and National Center for Biodefense and Infectious Diseases, George Mason University, MS1H8, Manassas, VA, 20110, USA.|Institute of Theoretical and Experimental Biophysics of the Russian Academy of Sciences, Pushchino, Moscow Region, 142290, Russia.
authors.forename: Victor N
authors.initials: VN
authors.lastname: Morozov
authors.affiliation: School of Systems Biology and National Center for Biodefense and Infectious Diseases, George Mason University, MS1H8, Manassas, VA, 20110, USA. mvanhoek@gmu.edu.
authors.forename: Monique L
authors.initials: ML
authors.lastname: van Hoek
mesh_terms: D000336:Aerosols / Q000008:administration & dosage*; D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage*; D005604:Francisella tularensis / Q000187:drug effects*; D064704:Levofloxacin / Q000008:administration & dosage*; D008081:Liposomes / Q000008:administration & dosage*; D008168:Lung / Q000382:microbiology; D051379:Mice; D008807:Mice, Inbred BALB C; D053758:Nanoparticles / Q000008:administration & dosage*; D014406:Tularemia / Q000188:drug therapy*
chemical_list: D000336:Aerosols; D000900:Anti-Bacterial Agents; D008081:Liposomes; D064704:Levofloxacin
keywords: Aerosol; Animal model; Francisella; Levofloxacin; Nanoaerosol; Pulmonary infection