Inhaled tacrolimus modulates pulmonary fibrosis without promoting inflammation in bleomycin-injured mice

P. Shivshankar, H. Payan, C. Calhoun, S. Levine, R. O. Williams, J. Jagirdar, J. I. Peters, C. Jourdan Le Saux

Research output: Contribution to journalArticle

3 Scopus citations

Abstract

No effective treatment is currently available for idiopathic pulmonary fibrosis (IPF) patients. Tacrolimus (Tac) has gained attention as a possible treatment due to its potent anti-fibrotic properties. Unfortunately, Tac induces multiple side effects including inflammation and renal insufficiency. We hypothesized that direct daily delivery of nebulized TaC-nanoparticle aggregates into the lungs (Tacinh) would not only prevent fibrosis but also limit systemic complications. C57B16IJ mice were given Tac by I. P. injection (TacIP) or Tacinh I h or 6 days after bleomycin injury. Residual inflammation and fibrosis were assessed in the lungs 21 days after bleomycin injury. Bleomycin-injured mice receiving Tacinh compared with those receiving TacIP had a higher survival (100 and 83 J %, respectively, vs. 49 %). Inflammation and fibrosis were significantly reduced in mice receiving Tacinh compared to mice receiving TacIP Tacinh may provide an effective and safer treatment for IPF. This finding revives the interest in this drug to treat IPF patients.

Original languageEnglish (US)
Pages (from-to)469-477
Number of pages9
JournalJournal of Drug Delivery Science and Technology
Volume24
Issue number5
DOIs
Publication statusPublished - Sep 1 2014

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Keywords

  • Inhalation drugs
  • Lung fibrosis
  • Nanoparticles
  • TGF-β signaling
  • Tacrolimus

ASJC Scopus subject areas

  • Pharmaceutical Science

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