title: Inhaled microparticles containing clofazimine are efficacious in treatment of experimental tuberculosis in mice.
abstract: Inhalable clofazimine-containing dry powder microparticles (CFM-DPI) and native clofazimine (CFM) were evaluated for activity against Mycobacterium tuberculosis in human monocyte-derived macrophage cultures and in mice infected with a low-dose aerosol. Both formulations resulted in 99% killing at 2.5 μg/ml in vitro. In mice, 480 μg and 720 μg CFM-DPI inhaled twice per week over 4 weeks reduced numbers of CFU in the lung by as much as log(10) 2.6; 500 μg oral CFM achieved a log(10) 0.7 reduction.
authors.affiliation: Pharmaceutics Division, CSIR-Central Drug Research Institute, Lucknow, India.
authors.forename: Rahul Kumar
authors.initials: RK
authors.lastname: Verma
authors.forename: Willem A
authors.initials: WA
authors.lastname: Germishuizen
authors.forename: M Portia
authors.initials: MP
authors.lastname: Motheo
authors.forename: Atul Kumar
authors.initials: AK
authors.lastname: Agrawal
authors.forename: Amit Kumar
authors.initials: AK
authors.lastname: Singh
authors.forename: Mradul
authors.initials: M
authors.lastname: Mohan
authors.forename: Pushpa
authors.initials: P
authors.lastname: Gupta
authors.forename: Umesh Datta
authors.initials: UD
authors.lastname: Gupta
authors.forename: Moloko
authors.initials: M
authors.lastname: Cholo
authors.forename: Ronald
authors.initials: R
authors.lastname: Anderson
authors.forename: P Bernard
authors.initials: PB
authors.lastname: Fourie
authors.forename: Amit
authors.initials: A
authors.lastname: Misra
mesh_terms: D000280:Administration, Inhalation; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use; D000995:Antitubercular Agents / Q000627:therapeutic use*; D002478:Cells, Cultured; D002991:Clofazimine / Q000627:therapeutic use*; D016503:Drug Delivery Systems; D008168:Lung / Q000382:microbiology; D008264:Macrophages / Q000187:drug effects / Q000382:microbiology; D051379:Mice; D008826:Microbial Sensitivity Tests; D009169:Mycobacterium tuberculosis / Q000187:drug effects*; D053758:Nanoparticles / Q000627:therapeutic use*; D016896:Treatment Outcome; D014376:Tuberculosis / Q000188:drug therapy*
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D000995:Antitubercular Agents; D002991:Clofazimine