Abdominal aortic aneurysms (AAAs) result from progressive elastic matrix degradation by matrix metalloproteases (MMPs) -2 & -9. Orally-delivered doxycycline (DOX) has been shown effective in slowing AAA growth in human & animal studies by limiting ECM degradation within through inhibition of MMP-2 & -9. However, systemic delivery and high circulating doses appear to have adverse side-effects'. DOX doses in the delivered μg/mL range also appear to inhibit elastic matrix deposition by vascular cells. Hence, we investigated a nanoparticle (NP)-based approach towards localized, controlled, & sustained DOX delivery to AAAs. We evaluated effects of (a) DOX released from NPs on elastic matrix synthesis & MMP-inhibition in rat AAA smooth muscle cell (EaRASMC) cultures, and (b) surface modification of these NPs with cationic amphiphiles on elastin binding and LOX activity, which mediates crosslinking of elastin into a mature matrix.
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