title: Respirable PLGA microspheres containing rifampicin for the treatment of tuberculosis: screening in an infectious disease model.
abstract: OBJECTIVE
  Targeted delivery of rifampicin loaded microspheres to the alveolar macrophage, the host cell for Mycobacterium tuberculosis (MTB), may be an effective targeted approach to pulmonary tuberculosis therapy. A guinea pig infection model has been adopted as a post-treatment screening method for antimicrobial effect. Insufflation and nebulization methods of drug delivery were evaluated.
  
  
  METHODS
  Rifampicin alone (RIF, 1.03-1.72 mg/kg), within poly(lactide-co-glycolide) microspheres (R-PLGA, equivalent to 1.03-1.72 mg/kg) or polymer microparticles alone (PLGA) were administered by insufflation or nebulization, 24 h before bacterial aerosol exposure. Animals were infected with an aerosol containing a small number (2 x 10(5) cfu/mL) of virulent H37Rv strain of MTB. Lung and spleen tissue samples were collected 28 days after infection for quantitative bacteriology and histopathological analysis.
  
  
  RESULTS
  There was a dose-effect relationship between insufflated R-PLGA and burden of bacteria in the lungs. In addition, guinea pigs treated with R-PLGA had a significantly smaller number of viable bacteria (P < 0.05), reduced inflammation and lung damage than lactose or saline control, PLGA or RIF treated animals.
  
  
  CONCLUSIONS
  These studies indicate the potential of R-PLGA, delivered by insufflation or nebulization directly to the lungs, to affect the early development of pulmonary TB.
authors.affiliation: School of Pharmacy, University of North Carolina, Chapel Hill 27599, USA.
authors.forename: S
authors.initials: S
authors.lastname: Suarez
authors.forename: P
authors.initials: P
authors.lastname: O'Hara
authors.forename: M
authors.initials: M
authors.lastname: Kazantseva
authors.forename: C E
authors.initials: CE
authors.lastname: Newcomer
authors.forename: R
authors.initials: R
authors.lastname: Hopfer
authors.forename: D N
authors.initials: DN
authors.lastname: McMurray
authors.forename: A J
authors.initials: AJ
authors.lastname: Hickey
mesh_terms: D000280:Administration, Inhalation; D000336:Aerosols; D000818:Animals; D000904:Antibiotics, Antitubercular / Q000008:administration & dosage* / Q000627:therapeutic use*; D015169:Colony Count, Microbial; D004305:Dose-Response Relationship, Drug; D004337:Drug Carriers; D004339:Drug Compounding; D016503:Drug Delivery Systems; D004353:Drug Evaluation, Preclinical; D006168:Guinea Pigs; D007202:Indicators and Reagents; D019344:Lactic Acid; D008168:Lung / Q000382:microbiology / Q000473:pathology; D008264:Macrophages / Q000378:metabolism; D008297:Male; D008826:Microbial Sensitivity Tests; D008863:Microspheres; D009169:Mycobacterium tuberculosis; D011100:Polyglycolic Acid; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011108:Polymers; D012293:Rifampin / Q000008:administration & dosage* / Q000627:therapeutic use*; D014376:Tuberculosis / Q000188:drug therapy* / Q000382:microbiology / Q000473:pathology
chemical_list: D000336:Aerosols; D000904:Antibiotics, Antitubercular; D004337:Drug Carriers; D007202:Indicators and Reagents; D011108:Polymers; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D012293:Rifampin