To help increase blood flow through vessels that are narrowed or partially blocked, surgeons insert tiny metal mesh tubes called stents. Once inserted, stents expand inside of blood vessels. Stents are often coated with antiproliferative drugs, such as paclitaxel, to reduce the chance of blood vessel blockages related to stent-induced injury. Though stents have significantly improved therapeutic outcomes, the drug eluted by a stent cannot be changed and drug doses cannot be modified or replenished. In an effort to address these challenges, a team of researchers tested whether they could deliver drugs to rats' injured blood vessels by using a uniform magnetic field to direct drug-loaded magnetic nanoparticles to stents in these blood vessels.

Credit: Floris Slooff

Robert Levy of The Children's Hospital of Philadelphia (PA) and his colleagues injured the left carotid arteries of anesthetized male Sprague-Dawley rats (Proc. Natl. Acad. Sci. USA published online 19 April 2010; doi:10.1073/pnas.0909506107). They then placed a stent into the left carotid artery of each rat and used ligatures to isolate the region of the artery encompassing the stent. One group of the animals was then exposed to a uniform magnetic field. Next, the research team delivered paclitaxel-loaded biodegradable magnetic nanoparticles to the isolated arterial segment of each rat for 30 seconds and then released the ligatures. The animals in the magnetic field treatment group were then exposed to the field for an additional 5 minutes.

Analyses revealed that 2 and 24 hours after stent insertion, there were substantially more magnetic nanoparticles in the stent and the surrounding arterial tissue in the rats that had been exposed to the magnetic field than in control rats that had not been exposed. The rats in the magnetic field exposure group that had received magnetic nanoparticles containing a 7.5-μg dose of paclitaxel showed significantly inhibited in-stent restenosis 14 days after the magnetic treatment. The nonmagnetic injection of drug-loaded magnetic nanoparticles with the same dose of paclitaxel did not significantly inhibit growth of new tissue.

These results show that a magnetic field targeting approach, similar to the one described by Levy and his team, could potentially be used to help reduce the risk of in-stent restenosis in humans. Levy and his colleagues suggest that by combining efficient targeting techniques with the sustained drug release properties of magnetic nanoparticles, researchers could develop a safer and more efficacious alternative for treating diseased or injured blood vessels.