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Drug-Delivery Particles Bring Obesity Fighting Drugs Straight to Fat Source

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The method allows anti-obesity medication to reach fat tissue without causing side effects elsewhere in the body. So far, the method has been tested on mice.

In the war against obesity, researchers from the Massachusetts Institute of Technology (MIT) and Brigham and Women’s Hospital have found a quick route to the front lines.

They’ve developed a delivery system, nanoparticles, that carries drugs directly to fat tissue, bypassing other parts of the body where the therapy could cause side effects.

Once there, the anti-obesity drugs convert fat-story cells into fat-burning ones, delivery a highly targeted dose that can work quickly to eliminate weight.

The system has thus far been tested in mice, but it has potential to give new uses to drugs used in diabetes—like rosiglitazone—that fell out of favor after they were linked to cardiovascular effects. With this method, the therapy is contained in 2 different polymers—the first to package the drugs, and the second to guide it to its target of proteins that line the blood vessels in adipose tissue.

Findings were published Monday in the Proceedings of the National Academy of Sciences.

“The advantage here is now you have a way of targeting it to a particular area and not giving the body systemic effects,” said Robert S. Langer, PhD, the David H. Koch Institute Professor at MIT and a senior author on the article. “You can get the positive effects that you’d want in terms of antiobesity but not the negative ones that sometimes occur.”

In earlier work, Langer and colleagues had shown the value of promoting new blood vessel growth in adipose tissue, which promotes weight loss in mice. Drugs that promote blood vessel growth can have harmful effects elsewhere, however. That’s where the nanoparticle strategy comes in.

By using the 2-part polymer delivery system, the researchers let the drugs directly attach to the proteins in adipose tissue, promoting the conversion of white adipose tissue to brown, leading to fat burning and weight loss in the mice.

After being treated with this method, the mice in their experiment lost about 10% of their body weight after becoming obese on a high fat diet.

Right now, this nanoparticle drug delivery system is only possible through injection, so it would be reserved for the severely obese, according to the researchers.

“For it to be broadly applicable for treatment of obesity, we would have to come up with easier ways to administer these targeted nanoparticles, such as orally," said Omid Farokhzad, MD, director of the Laboratory of Nanomedicine at Brigham & Women’s and the other senior author on the paper.

This method is challenging because nanoparticles require additional steps to penetrate intestinal lining if taken orally, but Langer and Farokhzad are working on that, too. They’ve developed a nanoparticle using transferrin, a protein used to bring iron through the body.

Reference

Yee Y, Xu X, Zhang XQ, Farokhzad OC, Langer RS. Preventing diet-induced obesity in mice by adipose tissue transformation and angiogenesis using targeted nanoparticles. PNAS. 2016; doi: 10.1073/pnas.1603840113.

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