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

• Published in: Biomaterials Vol. 31; no. 36; pp. 9554 - 9564
• Main Authors: Yamawaki-Ogata, A, Hashizume, R, Satake, M, Kaneko, H, Mizutani, S, Moritan, T, Ueda, Y, Narita, Y
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier Ltd 01.12.2010
• Subjects: Advanced Basic Science; Animals; Aorta - drug effects; Aorta - enzymology; Aorta - pathology; Aortic aneurysm; Aortic Aneurysm - blood; Aortic Aneurysm - drug therapy; Aortic Aneurysm - enzymology; Biocompatible Materials - pharmacology; Biocompatible Materials - therapeutic use; Chemokines - metabolism; Coculture Techniques; Delayed-Action Preparations; Dentistry; Disease Models, Animal; Doxycycline; Doxycycline - pharmacology; Doxycycline - therapeutic use; Drug delivery system; ECM; Elasticity - drug effects; Elastin; Elastin - metabolism; Gene Expression Regulation - drug effects; Intercellular Signaling Peptides and Proteins - metabolism; Lactic Acid - pharmacology; Lactic Acid - therapeutic use; Macrophages - cytology; Macrophages - drug effects; Macrophages - metabolism; Matrix metalloproteinase; Matrix Metalloproteinases - metabolism; Mice; Mice, Inbred C57BL; Microscopy, Electron, Scanning; Myocytes, Smooth Muscle - cytology; Myocytes, Smooth Muscle - drug effects; Myocytes, Smooth Muscle - metabolism; Polyesters; Polymers - pharmacology; Polymers - therapeutic use; Tissue Culture Techniques; Tissue Inhibitor of Metalloproteinases - metabolism; Matrix metalloproteinase; Aortic aneurysm; Drug delivery system; Elastin; ECM; Doxycycline
• ISSN: 0142-9612; 1878-5905
• DOI: 10.1016/j.biomaterials.2010.08.069

Abstract 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-β1 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-α 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.