Pharmaceutical Research

, Volume 26, Issue 8, pp 1847–1855

Formulation and Pharmacokinetics of Self-Assembled Rifampicin Nanoparticle Systems for Pulmonary Delivery

  • Jean C. Sung
  • Danielle J. Padilla
  • Lucila Garcia-Contreras
  • Jarod L. VerBerkmoes
  • David Durbin
  • Charles A. Peloquin
  • Katharina J. Elbert
  • Anthony J. Hickey
  • David A. Edwards
Research Paper

DOI: 10.1007/s11095-009-9894-2

Cite this article as:
Sung, J.C., Padilla, D.J., Garcia-Contreras, L. et al. Pharm Res (2009) 26: 1847. doi:10.1007/s11095-009-9894-2

Abstract

Purpose

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.

KEY WORDS

aerosolsantibioticsnanoparticlespulmonary drug deliverytuberculosis

Abbreviations

BAL

Bronchoalveolar lavage

DCM

Dichloromethane

FPFTD

Fine particle fraction of the total dose less than 5.8 μm

NP

Nanoparticles

PK

Pharmacokinetics

PLGA

Poly (lactide-co-glycolide)

PNAP

Porous nanoparticle-aggregate particle

PNAP40

PNAPs containing 40% NP by weight

PNAP80

PNAPs containing 80% NP by weight

PP

Porous particles

PVA

Poly(vinyl alcohol)

TB

Tuberculosis

Copyright information

© Springer Science+Business Media, LLC 2009

Authors and Affiliations

  • Jean C. Sung
    • 1
  • Danielle J. Padilla
    • 2
  • Lucila Garcia-Contreras
    • 2
  • Jarod L. VerBerkmoes
    • 1
  • David Durbin
    • 3
  • Charles A. Peloquin
    • 3
  • Katharina J. Elbert
    • 1
  • Anthony J. Hickey
    • 2
  • David A. Edwards
    • 1
  1. 1.Harvard School of Engineering and Applied SciencesCambridgeUSA
  2. 2.School of PharmacyUniversity of North Carolina at Chapel HillChapel HillUSA
  3. 3.National Jewish Medical and Research CenterDenverUSA