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Biomaterials. 2019 May;203:52-62. doi: 10.1016/j.biomaterials.2019.02.017. Epub 2019 Feb 22.

Hydrogel-based delivery of Il-10 improves treatment of bleomycin-induced lung fibrosis in mice.

Author information

1
Department of Medicine, Division of Pulmonary and Critical Care Medicine, Stanford University, Stanford, CA, 94305, USA.
2
Department of Materials Science and Engineering, Stanford University, Stanford, CA, 94305, USA; Department of Medicine, Division of Infectious Disease, Stanford University, Stanford, CA, 94305, USA.
3
Department of Medicine, Division of Infectious Disease, Stanford University, Stanford, CA, 94305, USA.
4
Department of Surgery, Division of Pediatric Surgery, Baylor College of Medicine and Texas Children's Hospital, Houston, TX, 77030, USA.
5
Department of Medicine, Division of Pulmonary and Critical Care Medicine, Stanford University, Stanford, CA, 94305, USA. Electronic address: vdejesus@stanford.edu.

Abstract

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.

KEYWORDS:

Drug delivery; Fibrosis; Hyaluronic acid; Hydrogel; Idiopathic pulmonary fibrosis; Interleukin-10

PMID:
30852423
PMCID:
PMC6430662
[Available on 2020-05-01]
DOI:
10.1016/j.biomaterials.2019.02.017

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