共 57 条
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
来源:
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.
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页码:52 / 62
页数:11
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