Synthesis and biological evaluation of a cross-linked hyaluronan-mitomycin C hydrogel.
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 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.
Li
Hao
H
Department of Medicinal Chemistry, The University of Utah, 419 Wakara Way, Suite 205, Salt Lake City, Utah 84108-125, USA.
Liu
Yanchun
Y
Shu
Xiao Zheng
XZ
Gray
Steven D
SD
Prestwich
Glenn D
GD
D000818:Animals; D001672:Biocompatible Materials; D005260:Female; D006801:Humans; D006820:Hyaluronic Acid / Q000737:chemistry*; D020100:Hydrogels / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy; D016685:Mitomycin / Q000737:chemistry*; D051381:Rats; D017208:Rats, Wistar
D001672:Biocompatible Materials; D020100:Hydrogels; D016685:Mitomycin; D006820:Hyaluronic Acid