Long-acting opioid antidote at single dose at the horizon

Recent reports have shown a 1,000% increase in opioid abuse (including fentanyl, a synthetic drug) in the United States over the last decade. In 2017, for example, there were 47,000 deaths attributed to an opioid overdose, according to the US Center for Disease Control and Prevention (CDC). Health officials have been alarmed by the increasing number of drug-related overdose deaths and the growing popularity of synthetic opiates.

Fentanyl is particularly dangerous as a recreational drug because of its long-lasting and rapidly occurring effects. This means that even a small amount of the drug could lead to overdose and its complications. Currently, antidotes such as naloxone are used to treat these overdoses and their effects are usually short-lived. Therefore, multiple doses of naloxone should be taken to control the persistent effects of fentanyl. Researchers are currently developing an antidote for fentanyl and opioids that would be sustainable and therefore, a single dose would be enough to treat overdoses. They used polymer nanoparticles to prolong the action of this antidote. The results of the study titled "Next-Generation Opioid Antidote: Covalent Nanoparticles for Delivery of Mu Opioid Antagonists" were presented at the 2019 Spring National Conference organized by the American Chemical Society (ACS) in Orlando on March 31, 2019.

Covalent nanoparticles (top) release naloxone (purple structures) slowly, in 24 hours. CREDIT: Marina Kovaliov

Saadyah Averick, a senior scientist and researcher in the field of biomaterials within the Allegheny Health Network Research Institute team in Pittsburgh, said: "We became interested in this problem as we tried to to manufacture non-addictive badgesics. During this research, we understood the limits of current opioid antidotes. Currently used opioids act as badgesics by acting on the mu opioid receptor (MOR) in the brain, Averick said. He said: "The medications bind, turn on the receiver and stimulate a euphoric feeling. Synthetic opioids, such as fentanyl, work very well. He explained that fentanyl is more dangerous because it has a more lasting effect and is absorbed by the fat tissue of the body. This makes its elimination of the body a difficulty. The drug continues to infiltrate into the bloodstream of adipose tissue and its effects therefore last for several hours. Naloxone acts as an antidote, but only has activity for half an hour to an hour, after which the dose should be repeated.

The team has attempted to address the challenge of creating a more sustainable antidote against more enduring opioids, such as fentanyl. They have developed a unique drug delivery system capable of providing a constant dose of antidote that can be administered for 24 hours. They took naloxone with its chemical structure at several cycles and combined it with polylactic acid (PLA) to create a polymer of naloxone. Then, they made covalent nanoparticles (CNP) by adding these polymers to a solution of polyvinyl alcohol. The final product had a diameter of about 300 nanometers. Averick said, "In collaboration with Benedict Kolber's laboratory at Duquesne University, research has shown that these nanoparticles can deliver enough naloxone in linear release form to block the badgesic effect of morphine for a long time." 24 hours. In a next step, the study will be extended to fentanyl. "

The team reported that, at present, their experiments were conducted on laboratory mice. Soon, when the safety of the antidote is established, it can be the subject of clinical trials. They are currently evaluating the release of naloxone by nanoparticles. Averick explained, "Ultimately, we hope to develop a therapeutic intervention against overdose of fentanyl that can be used in the field, perhaps replacing short-acting naloxone as an antidote." of choice for overdose. We anticipate that this drug delivery system will also be effective for other opioids other than fentanyl. The team believes that the molecule should be ready for the market in the next five years.