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

被引:83
作者
Shamskhou, Elya A. [1 ]
Kratochvil, Michael J. [2 ,3 ]
Orcholski, Mark E. [1 ]
Nagy, Nadine [3 ]
Kaber, Gernot [3 ]
Steen, Emily [4 ]
Balaji, Swathi [4 ]
Yuan, Ke [1 ]
Keswani, Sundeep [4 ]
Danielson, Ben [3 ]
Gao, Max [1 ]
Medina, Carlos [3 ]
Nathan, Abinaya [1 ]
Chakraborty, Ananya [1 ]
Bollyky, Paul L. [3 ]
Perez, Vinicio A. De Jesus [1 ]
机构
[1] Stanford Univ, Div Pulm & Crit Care Med, Dept Med, Stanford, CA 94305 USA
[2] Stanford Univ, Dept Mat Sci & Engn, Stanford, CA 94305 USA
[3] Stanford Univ, Dept Med, Div Infect Dis, Stanford, CA 94305 USA
[4] Texas Childrens Hosp, Baylor Coll Med, Dept Surg, Div Pediat Surg, Houston, TX USA
关键词
Interleukin-10; Hyaluronic acid; Fibrosis; Hydrogel; Drug delivery; Idiopathic pulmonary fibrosis; GROWTH-FACTOR-BETA; TGF-BETA; PULMONARY-FIBROSIS; INTERLEUKIN-10; GENE; INFLAMMATORY CYTOKINES; INJECTABLE HYDROGELS; I COLLAGEN; EXPRESSION; FIBROBLASTS; HYALURONAN;
D O I
10.1016/j.biomaterials.2019.02.017
中图分类号
R318 [生物医学工程];
学科分类号
0831 ;
摘要
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.
引用
收藏
页码:52 / 62
页数:11
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