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NIH Funding Nanodrugs to Prevent Opioid Addiction

Head in hands

(Photo by Cristian Newman on Unsplash)

15 Mar. 2019. A drug that invokes the immune system to block addictive effects of opioid pain drugs and heroin is in early development at Washington University in St. Louis. A team led by biomedical engineering professor Jai Rudra received a 2-year, $373,000 grant from National Institute on Drug Abuse, or NIDA, part of National Institutes of Health, to fund the research.

Rudra and colleagues at WashU aim to help fill a need for better treatment options to meet the growing and continuing public health emergency of prescription opioid drug abuse, as well as heroin and fentanyl sold on the street. Overdose deaths from these drugs this year number more than 130 per day, according to NIDA. A report by the National Academies of Sciences, Engineering, and Medicine in July 2017 spells out the full scope of the crisis beyond overdose deaths, with some 2 million Americans age 12 and older addicted to prescription opioid drugs and another 600,000 addicted to heroin.

Current opioid treatments use opioid analogues to help reduce cravings for the drugs, while also reducing withdrawal symptoms. And while they are often effective, these treatments also run the risk of feeding participants’ addictions. The WashU team proposes an alternative strategy: an immunotherapy drug, one that invokes the immune system, to block the addictive effects of opioids, to help individuals in treatment programs break their addiction habits, as well as prevent opioid overdoses.

“We are developing a therapy that will generate an anti-opioid antibody that will arrest the drug in circulation and prevent it from getting to the brain,” says Rudra in a university statement. “While this immunotherapy does not directly address the underlying neurobiological mechanism behind drug abuse, it is intended to treat a person in recovery in the event of a relapse. The patient will obtain no pleasure from taking the drug and will be further motivated to continue toward recovery.”

The WashU team plans to design low-weight drug molecules called haptens that can invoke an immune response. But unlike antigens — full-fledged proteins often designed for immunotherapies — haptens need a carrier, other protein-like molecules, to get the attention of the immune system. For that carrier, the researchers plan to use peptides, short chains of amino acids resembling small proteins, but with amphiphilic properties, which means they both repel and attract water. Because of these properties, peptide amphiphiles can form on their own into nanoscale rods and fibers, with bioactive effects.

The researchers propose creating haptens with analogs of the opioid pain drug oxycodone and heroin, and packaging them with peptide amphiphiles so they form nanoscale particles that invoke the immune system like a vaccine. “Since the immune system does not see the small drug molecules as a threat, we attach them to a synthetic supramolecular nanocarrier,” notes Rudra. “The carrier-drug combination is sensed by the immune system as a foreign entity, generating an anti-drug antibody response.”

The team plans to test the oxycodone and heroin vaccines separately in lab mice, but also try assembling one vaccine with this technology that prevents addiction to both substances. The researchers will measure the ability of the vaccines to prevent addiction in test mice, as well as in mice showing symptoms of opioid addiction.

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