Synthesis and biological evaluation of a cross-linked hyaluronan-mitomycin C hydrogel

被引:47
作者
Li, H [1 ]
Liu, YC [1 ]
Shu, XZ [1 ]
Gray, SD [1 ]
Prestwich, GD [1 ]
机构
[1] Univ Utah, Dept Med Chem, Salt Lake City, UT 84108 USA
关键词
D O I
10.1021/bm034463j
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
A cross-linked hyaluronan (HA) hydrogel that contained a covalently bound derivative of the anti-proliferative drug mitomycin C (MMC) was synthesized and evaluated in vitro and in vivo. The HA-MMC hydrogel was prepared by coupling MMC-aziridinyl-N-acrylate with thiol-modified HA followed by cross-linking C, with poly(ethylene glycol) diacrylate (PEGDA). MMC was released from 0.5% and 2.0% MMC films by hydrolysis in proportion to the MMC loading. When incubated in vitro with human T31 tracheal scar fibroblasts, 0.5% MMC films inhibited proliferation, whereas 2.0% MMC films were cytotoxic. When implanted in vivo into a rat peritoneal cavity, neither 0.5% nor 2.0% HA-MMC films elicited a severe peritoneal fluid leukocyte response. Importantly, MMC reduced the thickness of fibrous tissue formed surrounding the implanted films. Thus, cross-linked HA-MMC films have strong potential as anti-fibrotic barriers for the prevention of post-surgical adhesions.
引用
收藏
页码:895 / 902
页数:8
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