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

doi:10.1016/S1773-2247(14)50090-1

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

Department of Medicine

Producción científica: Article › revisión exhaustiva

4 Citas (Scopus)

Resumen

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 (Tac_inh) would not only prevent fibrosis but also limit systemic complications. C57B16IJ mice were given Tac by I. P. injection (Tac_IP) or Tac_inh 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 Tac_inh compared with those receiving Tac_IP had a higher survival (100 and 83 J %, respectively, vs. 49 %). Inflammation and fibrosis were significantly reduced in mice receiving Tac_inh compared to mice receiving Tac_IP Tac_inh may provide an effective and safer treatment for IPF. This finding revives the interest in this drug to treat IPF patients.

Idioma original	English (US)
Páginas (desde-hasta)	469-477
Número de páginas	9
Publicación	Journal of Drug Delivery Science and Technology
Volumen	24
N.º	5
DOI	https://doi.org/10.1016/S1773-2247(14)50090-1
Estado	Published - sept 1 2014

ASJC Scopus subject areas

Pharmaceutical Science

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title = "Inhaled tacrolimus modulates pulmonary fibrosis without promoting inflammation in bleomycin-injured mice",

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.",

keywords = "Inhalation drugs, Lung fibrosis, Nanoparticles, TGF-β signaling, Tacrolimus",

author = "P. Shivshankar and H. Payan and C. Calhoun and S. Levine and Williams, {R. O.} and J. Jagirdar and Peters, {J. I.} and {Jourdan Le Saux}, C.",

note = "Funding Information: We would like to thank Dr. Hazuda for her valuable comments and assistance in the writing of this manuscript. This study was financially supported by the IIMS, CTRC grant (Award Number UL 1RR025767) from the National Center for Research Resources, and the Janey Briscoe Center of Excellence in Cardiovascular Research Funds to Dr. CJLS; and National Institutes of Health grant (8UL1TR000149) to JIP.",

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AU - Shivshankar, P.

AU - Payan, H.

AU - Calhoun, C.

AU - Levine, S.

AU - Williams, R. O.

AU - Jagirdar, J.

AU - Peters, J. I.

AU - Jourdan Le Saux, C.

N1 - Funding Information: We would like to thank Dr. Hazuda for her valuable comments and assistance in the writing of this manuscript. This study was financially supported by the IIMS, CTRC grant (Award Number UL 1RR025767) from the National Center for Research Resources, and the Janey Briscoe Center of Excellence in Cardiovascular Research Funds to Dr. CJLS; and National Institutes of Health grant (8UL1TR000149) to JIP.

PY - 2014/9/1

Y1 - 2014/9/1

N2 - 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.

AB - 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.

KW - Inhalation drugs

KW - Lung fibrosis

KW - Nanoparticles

KW - TGF-β signaling

KW - Tacrolimus

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

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