Nanoparticles Could Replace Stents

(Ivanhoe Newswire) -- Researchers have developed targeted nanoparticles that can cling to artery walls and slowly release medicine, an advance that could provide an alternative to drug-releasing stents in some patients with cardiovascular disease.

The particles, dubbed "nanoburrs," are coated with tiny protein fragments that enable them to stick to target proteins and release their drug payload over several days. Omid Farokhzad, associate professor at Harvard Medical School, is quoted as saying that the nanoburr is one of the first such particles that can precisely hone in on damaged vascular tissue. Farokhzad and MIT Institute Professor Robert Langer, co-authors of the paper, have previously developed nanoparticles that seek out and destroy tumors.

The nanoburrs are targeted to a specific structure known as the basement membrane, which lines the arterial walls and is only exposed when the walls are damaged. The nanoburrs could deliver drugs to treat atherosclerosis and other inflammatory cardiovascular diseases.

In the current study, the team used paclitaxel, a drug that inhibits cell division and helps prevent the growth of 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," Langer was quoted as saying.

The researchers hope the particles will become a complementary approach that can be used with vascular stents, which are the standard of care for most cases of clogged and damaged arteries, or in lieu of stents in areas not well suited to them, such as near a fork in the artery.

The particles, which are spheres 60 nanometers in diameter, consist of three layers -- an inner core containing a complex of the drug and a polymer chain called PLA, a middle layer of soybean lecithin, a fatty material, and an outer coating of a polymer called PEG, which protects the particle as it travels through the bloodstream.

The drug is 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, so the researchers can control the timing of the drug's release by altering the chain length. So far, they have achieved drug release over 12 days in tests in cultured cells.

In tests in rats, the researchers showed that the nanoburrs can be injected intravenously into the tail and still reach their intended target — damaged walls of the left carotid artery. The nanoburrs bound to the damaged walls at twice the rate of non-targeted 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, lead author Juliana Chan was quoted as saying.

The nanoburrs may also prove useful in delivering drugs to tumors.
"This technology could have broad applications across other important diseases,” said Farokhzad, “including cancer and inflammatory diseases where vascular permeability or vascular damage is commonly observed."

SOURCE: Proceedings of the National Academy of Sciences, January 18, 2010

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