title: Formulation and pharmacokinetics of self-assembled rifampicin nanoparticle systems for pulmonary delivery.
abstract: OBJECTIVE
  To formulate rifampicin, an anti-tuberculosis antibiotic, for aerosol delivery in a dry powder 'porous nanoparticle-aggregate particle' (PNAP) form suited for shelf stability, effective dispersibility and extended release with local lung and systemic drug delivery.
  
  
  METHODS
  Rifampicin was encapsulated in PLGA nanoparticles by a solvent evaporation process, spray dried into PNAPs containing varying amounts of nanoparticles, and characterized for physical and aerosol properties. Pharmacokinetic studies were performed with formulations delivered to guinea pigs by intratracheal insufflation and compared to oral and intravenous delivery of rifampicin.
  
  
  RESULTS
  The PNAP formulations possessed properties suitable for efficient deposition in the lungs. In vitro release showed an initial burst of rifampicin, with the remainder available for release beyond eight hours. PNAPs delivered to guinea pigs by insufflation achieved systemic levels of rifampicin detected for six to eight hours. Moreover, rifampicin concentrations remained detectable in lung tissue and cells up to and beyond eight hours. Conversely, after pulmonary delivery of an aerosol without nanoparticles, rifampicin could not be detected in the lungs at eight hours.
  
  
  CONCLUSIONS
  Our results indicate that rifampicin can be formulated into an aggregated nanoparticle form that, once delivered to animals, achieves systemic exposure and extends levels of drug in the lungs.
authors.affiliation: Harvard School of Engineering and Applied Sciences, 29 Oxford Street, Pierce 322, Cambridge, Massachusetts 02138, USA.
authors.forename: Jean C
authors.initials: JC
authors.lastname: Sung
authors.forename: Danielle J
authors.initials: DJ
authors.lastname: Padilla
authors.forename: Lucila
authors.initials: L
authors.lastname: Garcia-Contreras
authors.forename: Jarod L
authors.initials: JL
authors.lastname: Verberkmoes
authors.forename: David
authors.initials: D
authors.lastname: Durbin
authors.forename: Charles A
authors.initials: CA
authors.lastname: Peloquin
authors.forename: Katharina J
authors.initials: KJ
authors.lastname: Elbert
authors.forename: Anthony J
authors.initials: AJ
authors.lastname: Hickey
authors.forename: David A
authors.initials: DA
authors.lastname: Edwards
mesh_terms: D000818:Animals; D000995:Antitubercular Agents / Q000008:administration & dosage / Q000737:chemistry* / Q000493:pharmacokinetics*; D002626:Chemistry, Pharmaceutical; D006168:Guinea Pigs; D019344:Lactic Acid; D053758:Nanoparticles; D011100:Polyglycolic Acid; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D012293:Rifampin / Q000008:administration & dosage / Q000737:chemistry* / Q000493:pharmacokinetics*
chemical_list: D000995:Antitubercular Agents; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D012293:Rifampin