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January 21, 2010
4 Min Read
After clinging to arterial walls, nanoburrs release drugs for preventing the formation of scar tissue that can clog arteries.
Using nanoparticle technology, researchers from the Massachusetts Institute of Technology (MIT; Cambridge MA) and Harvard University (Cambridge, MA) have designed new particles that can cling to damaged artery walls and slowly release medicine, opening a front in the war against cardiovascular disease.Called "nanoburrs," the particles are coated with tiny protein fragments that enable them to stick to damaged arterial walls. Once there, they can release drugs such paclitaxel, which inhibits cell division and helps prevent the growth of the scar tissue that can clog arteries. "This is a very exciting example of nanotechnology and cell targeting in action that I hope will have broad ramifications," says MIT professor Robert Langer, senior author of "Spatiotemporal Controlled Delivery of Nanoparticles to Injured Vasculature," appearing in the Proceedings of the National Academy of Sciences.Currently, one of the standard ways to treat clogged and damaged arteries is by implanting a vascular stent, which holds the artery open and releases drugs. The researchers hope that their new nanoburrs could be used alongside such stents--or in lieu of them--to treat damage located in areas not well suited to stents, such as near a fork in an artery.Langer and Omid Farokhzad, associate professor at Harvard Medical School and another senior author of the paper, have previously developed nanoparticles that seek out and destroy tumors. Their nanoburrs, however, are among the first particles that can zero in on damaged vascular tissue. They target a structure known as the basement membrane, which lines the arterial walls but is only exposed when the walls are damaged. To build their nanoparticles, the scientists screened a library of short peptide sequences to find one that binds most effectively to molecules on the surface of the basement membrane. The most successful one, a seven-amino-acid sequence called C11, was used to coat the outer layer of the nanoparticles.The inner core of the 60-nm-diameter particles carries the drug, which is bound to a polymer chain called PLA. A middle layer of soybean lecithin, a fatty material, lies between the core and the outer shell, which consists of a polymer called PEG that protects the particles as they travel through the bloodstream.The drug can be released only when it detaches from the PLA polymer chain, which occurs gradually by a reaction called ester hydrolysis. The longer the polymer chain, the longer this process takes, enabling the researchers to control the timing of the drug's release by altering the chain length. In tests in cultured cells, they have achieved drug release over 12 days.Uday Kompella, professor of pharmaceutical sciences at the University of Colorado, says the nanoburr's structure could make it easier to manufacture because the targeted peptides are attached to an outer shell and not directly to the drug-carrying core, which would require a more complicated chemical reaction. The design also reduces the risk of the nanoparticles bursting and releasing drugs prematurely, says Kompella, who was not involved in this research.Another advantage of the nanoburrs is that they can be injected intravenously at a site distant from the damaged tissue. In tests involving rats, the researchers showed that nanoburrs injected near the tail are able to reach their intended target--the walls of the injured carotid artery but not normal carotid artery. The burrs bound to the damaged walls at twice the rate of nontargeted nanoparticles.Because the particles can deliver drugs over a longer period of time and can be injected intravenously, patients would not have to endure repeated and surgically invasive injections directly into the area that requires treatment, says Juliana Chan, a graduate student in Langer's lab and lead author of the paper.The team is now testing the nanoburrs in rats over a two-week period to determine the most effective dose for treating damaged vascular tissue. The particles may also prove useful in delivering drugs to tumors. "This technology could have broad applications across other important diseases, including cancer and inflammatory diseases where vascular permeability or vascular damage is commonly observed," Farokhzad says.
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