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

Research output: Contribution to journal › Article › peer-review

4 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 (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.

Original language	English (US)
Pages (from-to)	469-477
Number of pages	9
Journal	Journal of Drug Delivery Science and Technology
Volume	24
Issue number	5
DOIs	https://doi.org/10.1016/S1773-2247(14)50090-1
State	Published - Sep 1 2014

Keywords

Inhalation drugs
Lung fibrosis
Nanoparticles
TGF-β signaling
Tacrolimus

ASJC Scopus subject areas

Pharmaceutical Science

Access to Document

10.1016/S1773-2247(14)50090-1

Cite this

@article{e9712771f7624541b1b4be9be975006a,

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.",

year = "2014",

month = sep,

day = "1",

doi = "10.1016/S1773-2247(14)50090-1",

language = "English (US)",

volume = "24",

pages = "469--477",

journal = "Journal of Drug Delivery Science and Technology",

issn = "1773-2247",

publisher = "Editions de Sante",

number = "5",

}

TY - JOUR

T1 - Inhaled tacrolimus modulates pulmonary fibrosis without promoting inflammation in bleomycin-injured mice

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

UR - http://www.scopus.com/inward/record.url?scp=84908363021&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84908363021&partnerID=8YFLogxK

U2 - 10.1016/S1773-2247(14)50090-1

DO - 10.1016/S1773-2247(14)50090-1

M3 - Article

AN - SCOPUS:84908363021

SN - 1773-2247

VL - 24

SP - 469

EP - 477

JO - Journal of Drug Delivery Science and Technology

JF - Journal of Drug Delivery Science and Technology

IS - 5

ER -

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

Abstract

Keywords

ASJC Scopus subject areas

Access to Document

Other files and links

Fingerprint

Cite this