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Targeting stents with local delivery of paclitaxel-loaded magnetic nanoparticles using uniform fields
Michael Chorny, Ilia Fishbein, Benjamin B. Yellen, Ivan S. Alferiev, Marina Bakay, Srinivas Ganta, Richard Adamo, Mansoor Amiji, Gary Friedman, Robert J. Levy and Alexander M. Klibanov
Proceedings of the National Academy of Sciences of the United States of America
Vol. 107, No. 18 (May 4, 2010), pp. 8346-8351
Published by: National Academy of Sciences
Stable URL: http://www.jstor.org/stable/25665541
Page Count: 6
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The use of stents for vascular disease has resulted in a paradigm shift with significant improvement in therapeutic outcomes. Polymer-coated drug-eluting stents (DES) have also significantly reduced the incidence of reobstruction post stenting, a disorder termed in-stent restenosis. However, the current DESs lack the capacity for adjustment of the drug dose and release kinetics to the disease status of the treated vessel. We hypothesized that these limitations can be addressed by a strategy combining magnetic targeting via a uniform field-induced magnetization effect and a biocompatible magnetic nanoparticle (MNP) formulation designed for efficient entrapment and delivery of paclitaxel (PTX). Magnetic treatment of cultured arterial smooth muscle cells with PTX-loaded MNPs caused significant cell growth inhibition, which was not observed under nonmagnetic conditions. In agreement with the results of mathematical modeling, significantly higher localization rates of locally delivered MNPs to stented arteries were achieved with uniform-field—controlled targeting compared to nonmagnetic controls in the rat carotid stenting model. The arterial tissue levels of stent-targeted MNPs remained 4- to 10-fold higher in magnetically treated animals vs. control over 5 days post delivery. The enhanced retention of MNPs at target sites due to the uniform field-induced magnetization effect resulted in a significant inhibition of in-stent restenosis with a relatively low dose of MNP-encapsulated PTX (7.5 μg PTX/stent). Thus, this study demonstrates the feasibility of site-specific drug delivery to implanted magnetizable stents by uniform field-controlled targeting of MNPs with efficacy for in-stent restenosis.
Proceedings of the National Academy of Sciences of the United States of America © 2010 National Academy of Sciences