期刊
BIOMATERIALS
卷 203, 期 -, 页码 52-62出版社
ELSEVIER SCI LTD
DOI: 10.1016/j.biomaterials.2019.02.017
关键词
Interleukin-10; Hyaluronic acid; Fibrosis; Hydrogel; Drug delivery; Idiopathic pulmonary fibrosis
资金
- Pulmonary Fibrosis Foundation IM Rosenzweig Award
- NIH [R01 HL134776, R01 HL134776-02, R03 HL133423-01]
- AHA Beginning Grant in Aid
- Stanford Cardiovascular Institute (CVI)
- Translational Research and Applied Medicine (TRAM)
- American Heart Association Scientist Development Grant [15SDG25710448]
- Parker B. Francis Fellowship
- Pulmonary Hypertension Association Proof of Concept Award
- Stanford ChEM-H Interdisciplinary Postdoctoral Training Program in Quantitative Mechanobiology
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-beta 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.
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