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.

Biomaterials
|October 5, 2010
PubMed

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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