Formulation and pharmacokinetics of self-assembled rifampicin nanoparticle systems for pulmonary delivery.
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.
Sung
Jean C
JC
Harvard School of Engineering and Applied Sciences, 29 Oxford Street, Pierce 322, Cambridge, Massachusetts 02138, USA.
Padilla
Danielle J
DJ
Garcia-Contreras
Lucila
L
Verberkmoes
Jarod L
JL
Durbin
David
D
Peloquin
Charles A
CA
Elbert
Katharina J
KJ
Hickey
Anthony J
AJ
Edwards
David A
DA
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*
D000995:Antitubercular Agents; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D012293:Rifampin