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Nanocurry vs. Cancer

Researchers hope that curcumin encapsulated in nanospheres will spice up clinical trials for Alzheimer’s, cystic fibrosis, and cancer.

In recent years, laboratory and animal studies have suggested that curcumin–the pigment that gives the Indian curry spice turmeric its bright-yellow hue–may have some power to kill tumors and clear the brain plaques that characterize Alzheimer’s disease.

Favored curry: Ordinary curcumin, shown at left in a vial of water, is hydrophobic and not readily absorbed into the bloodstream. At right is a water solution containing something better: curcumin encapsulated in 50-nanometer spheres that are far more easily absorbed and could allow lower doses in medical trials.

But because curcumin is insoluble, it mostly passes through the gut without making it into the bloodstream. While doctors in the United States, Europe, and Asia have conducted more than two-dozen clinical trials using curcumin, most have required patients to swallow up to 12 grams, or even more, of curcumin every day. That’s a lot–even for the most ardent lovers of Indian food.

Now researchers at the Johns Hopkins University School of Medicine and the University of Delhi, in India, have invented curcumin-carrying nanospheres that could far more easily slip into the bloodstream.

Call it nanocurry–a marriage of 21st-century nanotechnology with an ancient ingredient from the East. The nanospheres open up the possibility that low doses of oral curcumin could be used far more widely in clinical trials, a key step toward getting the ingredient from the spice aisle to the pharmacist’s shelf.

Animal studies to determine whether nanocurcumin has any effect against pancreatic tumors in mice are expected to begin within weeks; the development of the particles was published in the Journal of Nanobiotechnology in April.

Anirban Maitra, a professor of pathology and oncology at Johns Hopkins, and his collaborators in Delhi–including his father, Amarnath Maitra, a professor of chemistry–used special polymers to synthesize tiny nanoparticles about 50 nanometers in diameter. The particles have hydrophobic interiors and hydrophilic exteriors. The hydrophobic component holds the curcumin, while the hydrophilic exteriors make the particles soluble. This way, they can pass easily from the gut to the bloodstream. Once in the blood, the curcumin leaks out as the polymers slowly degrade.

The Johns Hopkins team has already shown in laboratory experiments with pancreatic cancer cells that nanocurcumin retains its ability to activate key events that destroy tumors. What’s more, early animal studies have revealed that the nanoparticles are nontoxic, the team says.

There’s a big need for these little particles. Over the past five years, evidence of curcumin’s clinical potential has steadily mounted. Studies in the United States, India, and elsewhere have shown that curcumin can fight tumor growth in breast, colon, ovarian, and pancreatic cancers.

Curcumin has also shown promise beyond fighting cancer: earlier this year, researchers at Massachusetts General Hospital reported that in mice, curcumin cleared and reduced plaques associated with Alzheimer’s disease.

Two years ago, a University of California, Los Angeles, team generated other data suggesting that curcumin may be able to treat and prevent Alzheimer’s disease. And three years ago, pediatricians at the Yale University School of Medicine showed in animal studies that curcumin can correct a defect associated with a chloride channel in cells that causes the most common form of cystic fibrosis.

“Even with existing free curcumin, we’re seeing very encouraging results,” says Bharat Bhushan Aggarwal, professor in the department of experimental therapeutics at the University of Texas MD Anderson Cancer Center and a cofounder of Curry Pharmaceuticals of Research Triangle Park, NC, which is developing curcumin-based drugs.

Over the past year, animal experiments at the Anderson center have demonstrated the efficacy of curcumin in its free form against tumors of the bladder, pancreas, ovaries, and brain.

Aggarwal and his colleagues have also tested curcumin in patients with lung cancer, pancreatic cancer, and multiple myeloma–a type of leukemia–with what he considers encouraging results. “We also know that even in high doses of up to 12 grams per day for several months, curcumin is very, very safe,” Aggarwal says. In addition, his team demonstrated earlier this year that curcumin has the ability to enhance the antitumor effect of drugs used to treat pancreatic and bladder cancers.

Such promises notwithstanding, curcumin has yet to be more widely embraced by the medical community because its insoluble form demands high doses. “The single most important reason for the limited use of turmeric in human clinical trials is its poor solubility,” Maitra says. Among other things, patients find the aftertaste of huge curcumin doses unbearable.

Now Maitra and his colleagues are about to begin new animal studies in which they will pit nanocurcumin against pancreatic cancer, cystic fibrosis, and Alzheimer’s disease. “Nanocurcumin is expected to dramatically improve the clinical potential of this promising drug,” says Maitra. And he says that someday, curcumin nanospheres could be decorated with special molecules that have an affinity for cancer cells, allowing the curcumin to home in on specific tumors.

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