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A doxycycline loaded, controlled-release, biodegradable fiber for the treatment of aortic aneurysms

  作者 Yamawaki-Ogata, A; Hashizume, R; Satake, M; Kaneko, H; Mizutani, S; Moritan, T; Ueda, Y; Narita, V  
  选自 期刊  BIOMATERIALS;  卷期  2010年31-36;  页码  9554-9564  
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[摘要]The pathogenesis of aortic aneurysm (AA) is characterized by degradation of extracellular matrix with Increased matrix metalloproteinases (MMPs) and inflammatory reaction Doxycycline (DOXY) has been reported to control the extension of AA by regulation of MMP However systemic administration may cause adverse side effects In this study we demonstrated the possibility of local administration of DOXY controlled-release biodegradable fiber (DCRBF) for AA in mice DCRBF was fabricated by biodegradable polymer (polylactic acid PLA) mixed with DOXY using an electrospinning technique DCRBF was cocultured with SMCs macrophages and aortic tissue and placed on an abdominal aortic aneurysm which induced apolipoprotein E-deficient mice We evaluated gene and protein expression of proteases elastin and inflammatory markers In the presence of DCRBF MMP-12 was significantly decreased TGF-beta 1 and Lox were significantly increased in SMC gene expression MMP-9 and -12 significantly decreased gene expression of macrophages The DCRBF preserved elastin content and decreased MMP-2 and -9 in aortic tissue In addition IGF-1 and TIMP-1 were significantly increased and IL-6 and TNF-alpha were significantly decreased with DCRBF in vivo In conclusion our results suggested that local administration of DCRBF may become a promising alternative therapeutic strategy for AA (C) 2010 Elsevier Ltd All rights reserved

 
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