Hydrogel-based delivery of Il-10 improves treatment of bleomycin-induced lung fibrosis in mice.
Drug delivery
Fibrosis
Hyaluronic acid
Hydrogel
Idiopathic pulmonary fibrosis
Interleukin-10
Journal
Biomaterials
ISSN: 1878-5905
Titre abrégé: Biomaterials
Pays: Netherlands
ID NLM: 8100316
Informations de publication
Date de publication:
05 2019
05 2019
Historique:
received:
19
09
2018
revised:
12
02
2019
accepted:
14
02
2019
pubmed:
11
3
2019
medline:
7
7
2020
entrez:
11
3
2019
Statut:
ppublish
Résumé
Idiopathic pulmonary fibrosis (IPF) is a life-threatening progressive lung disorder with limited therapeutic options. While interleukin-10 (IL-10) is a potent anti-inflammatory and anti-fibrotic cytokine, its utility in treating lung fibrosis has been limited by its short half-life. We describe an innovative hydrogel-based approach to deliver recombinant IL-10 to the lung for the prevention and reversal of pulmonary fibrosis in a mouse model of bleomycin-induced lung injury. Our studies show that a hyaluronan and heparin-based hydrogel system locally delivers IL-10 by capitalizing on the ability of heparin to reversibly bind IL-10 without bleeding or other complications. This formulation is significantly more effective than soluble IL-10 for both preventing and reducing collagen deposition in the lung parenchyma after 7 days of intratracheal administration. The anti-fibrotic effect of IL-10 in this system is dependent on suppression of TGF-β driven collagen production by lung fibroblasts and myofibroblasts. We conclude that hydrogel-based delivery of IL-10 to the lung is a promising therapy for fibrotic lung disorders.
Identifiants
pubmed: 30852423
pii: S0142-9612(19)30108-5
doi: 10.1016/j.biomaterials.2019.02.017
pmc: PMC6430662
mid: NIHMS1523478
pii:
doi:
Substances chimiques
Hydrogels
0
Bleomycin
11056-06-7
Interleukin-10
130068-27-8
Hyaluronic Acid
9004-61-9
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
52-62Subventions
Organisme : NIAID NIH HHS
ID : T32 AI007290
Pays : United States
Organisme : NHLBI NIH HHS
ID : R03 HL133423
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL139664
Pays : United States
Organisme : NIGMS NIH HHS
ID : R01 GM111808
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL134776
Pays : United States
Informations de copyright
Copyright © 2019 Elsevier Ltd. All rights reserved.
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