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A new nanoparticle approach
11-04-2019
by DDNews Staff  |  Email the author
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NEW YORK—An international team of researchers has used nanoparticles to deliver a drug that previously failed in clinical trials for pain into specific compartments of nerve cells, dramatically increasing its ability to treat pain in mice and rats. The findings have been published today in Nature Nanotechnology.
 
“We have taken a drug—an FDA-approved anti-vomiting medication—and using a novel delivery method, improved its efficacy and duration of action in animal models of inflammatory pain and neuropathic pain,” said Nigel Bunnett, Ph.D., chair of the department of Basic Science and Craniofacial Biology at New York University (NYU) College of Dentistry, and the study’s senior author. “The discovery that nanoparticle encapsulation enhances and prolongs pain relief in laboratory animals provides opportunities for developing much-needed non-opioid therapies for pain.”
  
Bunnett and his colleagues study G protein-coupled receptors, which are the target of one third of clinically used drugs. While it was thought that receptors function at the surface of nerve cells, they discovered that activated receptors move within the cell to a compartment called the endosome. In an endosome, receptors continue to function for prolonged periods.
 
“The sustained activity of receptors in endosomes drives pain,” Bunnett explained. 
 
In the Nature Nanotechnology study, researchers at NYU College of Dentistry, Monash University, Columbia University and the University of Santiago in Chile focused on a G protein-coupled receptor called the neurokinin 1 receptor. 
 
“Major pharmaceutical companies had programs to develop neurokinin receptor antagonists for chronic diseases, including pain and depression. However, in human trials, things fell apart. The neurokinin receptor is the poster child for failures in drug discovery to treat pain,” noted Bunnett.
 
The researchers suspected that these drugs failed to work because they were designed to block receptors at the surface of cells rather than in endosomes. So Bunnett and his colleagues encapsulated into nanoparticles a neurokinin receptor blocker called aprepitant, an FDA-approved drug used to prevent nausea and vomiting which failed clinical trials as a pain medication.
 
The nanoparticles were designed to enter nerves that transmit pain signals and release their aprepitant cargo in endosomes containing the neurokinin receptor. Nanoparticle-delivered aprepitant treated pain in mice and rats more completely and for longer periods than did conventional therapies, including opioids. And nanoparticle delivery minimized the dose of medication needed to treat the pain, which could be useful in avoiding side effects.
 
“The process we’ve developed is essentially like giving a drug infusion into the endosome of the cell,” Bunnett added. “By delivering a previously ineffective pain drug to the right compartment within the cell, it became highly effective as a pain treatment.” 
 
The researchers will continue to study the use of nanoparticles in delivering non-opioid pain medication, including developing ways to target them only to nerve cells that sense pain, which would allow for even smaller doses of the drug. They are also exploring encapsulating multiple drugs that block pain receptors, which could further improve the efficacy of treatment. The researchers note that additional studies are needed before nanoparticle-delivered pain medication can be tested in humans. 
 
Code: E11041901

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