New York University partnered with an international research team to study the use of nanoparticles to deliver a non-opioid-based drug—one 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.
With the findings recently published in Nature Nanotechnology, the team sought to investigate alternatives to opioids, a class of drugs used to treat pain. Opioids carry a high risk for addiction and overdose. Moreover, due to tolerance, their effectiveness diminishes over time, requiring growing doses to manage pain. Side effects of opioids include constipation and suppressing breathing, and only worsen as doses are increased.
Nigel Bunnett, PhD, chair of the Department of Basic Science and Craniofacial Biology at New York University, (NYU) College of Dentistry and the study’s author and colleagues studied G protein-coupled receptors, which are the target on 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. Professor Bunnett noted, “The sustained activity of receptors in endosomes drives pain.”
In their study published in Nature Nanotechnology, researchers at NYU College of Dentistry, Monash University, Columbia University, and the University of Santiago in Chile focused on G protein-coupled receptor called the neurokinin 1 receptor. Interestingly neurokinin receptor antagonists for chronic diseases were a focus of the pharmaceutical industry. But the clinical trials testing these targets failed miserably. The investigators suggest that the drugs failed to work because they were designed to block receptors at the surface of cells rather than in endosomes.
Repurposing an anti-vomiting medication with novel delivery method
Hence the team turned to nanoparticles—microscopic vehicles used for delivering drugs. Bunnett and his colleagues encapsulated into nanoparticles, a neurokinin receptor blocker called aprepitant, an FDA-approved drug used to prevent nausea and vomiting that failed clinical trials as pain medication. As professor Bunnett noted, “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.” He continued, “The process we’ve developed is essentially like giving a drug infusion into the endosome of the cell.” Thus, “By delivering a previously ineffective pain drug to the right compartment within the cell, it became highly effective as a pain treatment.”
More Preclinical research in hope of moving to Human Studies
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 also are inquiring into 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.
The study was funded by the National Institutes of Health (NIH); the Department of Defense (DOD) and National Health and Medical Research Council; the Australian Research Council and Takeda Pharmaceuticals, Inc.
Nigel Bunnett, PhD, chair of the Department of Basic Science and Craniofacial Biology at New York University, (NYU) College of Dentistry
Call to Action: This research team could be onto an innovative way to use nanoparticles to support new delivery for repurposed drugs for heretofore not possible pain management results. TrialSite News will continue to track this effort.Source: EurekAlert!