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Doxycycline Loaded Collagen-Chitosan Composite Scaffold for the Accelerated Healing of Diabetic Wounds
Published on: August 21, 2021
A doxycycline loaded, controlled-release, biodegradable fiber for the treatment of aortic aneurysms
A Yamawaki-Ogata1, R Hashizume, M Satake
1Department of Cardiac Surgery, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8550, Japan.
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.
Insights
Local delivery of doxycycline controlled-release biodegradable fiber (DCRBF) effectively treats aortic aneurysms (AA) in mice by reducing inflammation and preserving tissue. This localized approach offers a promising alternative to systemic drug administration for AA.
Area of Science:
- Biomaterials Science
- Vascular Biology
- Pharmacology
Background:
- Aortic aneurysm (AA) pathogenesis involves extracellular matrix degradation and inflammation, with matrix metalloproteinases (MMPs) playing a key role.
- Systemic doxycycline (DOXY) can control AA by regulating MMPs but may cause adverse effects.
- Local drug delivery strategies are being explored to enhance therapeutic efficacy and minimize side effects for AA treatment.
Purpose of the Study:
- To investigate the potential of a locally administered doxycycline controlled-release biodegradable fiber (DCRBF) for treating aortic aneurysms (AA) in a mouse model.
- To evaluate the efficacy of DCRBF in modulating protease activity, inflammation, and extracellular matrix components in AA.
Main Methods:
- DCRBF was fabricated using electrospinning of polylactic acid (PLA) and DOXY.
- DCRBF was tested in vitro with smooth muscle cells (SMCs), macrophages, and aortic tissue, and in vivo on abdominal aortic aneurysms in apolipoprotein E-deficient mice.
- Gene and protein expression of proteases (MMPs), elastin, inflammatory markers (IL-6, TNF-α), and growth factors (IGF-1, TGF-β1) were analyzed.
Main Results:
- Local DCRBF administration significantly decreased MMP-12 in SMCs and MMP-9/-12 in macrophages.
- DCRBF treatment increased TGF-β1 and Lox gene expression in SMCs.
- In aortic tissue, DCRBF preserved elastin content and reduced MMP-2 and -9 levels, while in vivo studies showed increased IGF-1 and TIMP-1 and decreased IL-6 and TNF-α.
Conclusions:
- Local administration of DCRBF demonstrates significant therapeutic potential for aortic aneurysms.
- DCRBF effectively modulates key molecular pathways involved in AA pathogenesis, including protease activity and inflammation.
- This localized delivery system presents a promising alternative therapeutic strategy for AA, potentially overcoming limitations of systemic drug administration.
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