Targeting stents with local delivery of paclitaxel-loaded magnetic nanoparticles using uniform fields
Open accessAbstract
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.
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In a follow-up study using the same experimental setup, magnetic nanoparticles loaded with paclitaxel for local delivery resulted in a substantial reduction in restenosis with low doses of paclitaxel.
“In a follow-up study using the same experimental setup, the group used magnetic nanoparticles loaded with paclitaxel for local delivery, and they observed a substantial reduction in restenosis with low doses of paclitaxel103.”
From Perspectives and opportunities for nanomedicine in the management of atherosclerosis (2011) · cites this paper as [103]
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Self-citation
- Authors
- Chorny, M., Fishbein, I., Yellen, B. B., Alferiev, I. S., Bakay, M., Ganta, S., Adamo, R., Amiji, M., Friedman, G., & Levy, R. J.
- Affiliations
- Children's Hospital of Philadelphia (US)
- Duke University (US)
- Northeastern University (US)
- Drexel University (US)
- Corresponding author
- Levy, Robert J.
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2010-04-19
- Volume
- 107
- Issue
- 18
- Pages
- 8346-8351
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC2889533
- OpenAlex
- W2154590970
- Cited by
- 197
- References
- 30
- Citations by year
- 2026: 4 · 2025: 6 · 2024: 9 · 2023: 6 · 2022: 9 · 2021: 12 · 2020: 6 · 2019: 10 · 2018: 13 · 2017: 17 · 2016: 18 · 2015: 8 · 2014: 20 · 2013: 16 · 2012: 21
- FWCI
- 7.73
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- American Heart Association
- Children's Hospital of Philadelphia
- National Institutes of Health
- National Heart, Lung, and Blood Institute (T32HL007915)
- Topics
- Physical Sciences › Materials Science › Biomaterials › Nanoparticle-Based Drug Delivery
- Physical Sciences › Engineering › Biomedical Engineering › Characterization and Applications of Magnetic Nanoparticles
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmaceutical Science › Advanced Drug Delivery Systems
- Keywords
- drug-eluting stents, paclitaxel, magnetic nanoparticles, magnetic targeting, uniform magnetic field, in-stent restenosis, local drug delivery, arterial smooth muscle cells, carotid artery stenting, nanoparticle retention, vascular disease
- MeSH terms
- Animals, Cell Line, Graft Occlusion, Vascular, Magnetics, Male, Stents, Drug Delivery Systems, Rats, Sprague-Dawley, Paclitaxel, Microscopy, Electron, Transmission, Cell Proliferation, Rats, Metal Nanoparticles
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