Targeted Nanoparticles Inhibit Plaque Formation

Very low doses of fumagillin administered by this route in a rabbit model resulted in 60-80% reduction in the number of new blood vessels formed in plaques.

Investigators at the Washington University School of Medicine (St. Louis, MO, USA) created a model for atherosclerosis by feeding rabbits a high-cholesterol diet for 80 days. Evaluation of the rabbits by magnetic resonance imaging (MRI) showed that the animals' aortas contained many small atherosclerotic plaques.

An experimental drug was prepared by incorporating fumagillin into nanoparticles that were sensitized to specifically bind to integrin, a protein that is present in the base of the growing plaques. The animals were injected with nanoparticles that incorporated a dose of fumagillin 50,000 times lower than the concentration normally required to inhibit formation of new blood vessels.

Results reported in the July 6, 2006, online edition of Arteriosclerosis, Thrombosis, and Vascular Biology revealed that after treatment with integrin-targeted fumagillin-containing nanoparticles, the rabbits showed decreased MRI enhancement (2.9%) as compared to untreated rabbits (18.1%). In a third group of rabbits, non-targeted fumagillin nanoparticles did not alter vascular integrin expression (12.4%) when compared to the no-drug control. In a second study focused on microscopic changes, fewer microscopic blood vessels in the fumagillin-treated rabbit aorta were counted compared with control rabbits.

"We wanted to go after the early stages of the disease when patients do not yet need immediate intervention to prevent serious cardiac problems,” explained first author Dr. Patrick Winter, assistant professor of medicine at the Washington University School of Medicine. "We think fumagillin nanoparticles potentially could be incorporated into a protocol that includes lipid-lowering statin drugs or dietary changes. Fumagillin can have neurocognitive side effects, causing injury to the brain at high doses. The ability of the nanoparticles to concentrate the drug at the disease site allows the dose to be lowered.”



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