Single-dose antidotes for opioid overdose in the offing

Scientists are developing next-generation single-dose, longer-lasting antidotes for opioid overdose using polymer nanoparticles.

The US opioid epidemic is being driven by an unprecedented surge in deaths from fentanyl and other synthetic opiates, according to researchers who presented their results at the American Chemical Society (ACS) Spring 2019 National Meeting & Exposition in Orlando.

Fentanyl's powerful effects are long-lasting, and even tiny amounts of the drug can lead to an overdose.

Antidotes, such as naloxone, do not last long enough in the body to fully counter the drug, requiring repeated injections.

"We became interested in this problem while trying to make non-addictive pain medications," said Saadyah Averick, a scientist at Allegheny Health Network Research Institute in the US.

"In that course of research, we realised the limitations of current opioid antidotes,"Averick said in a statement.

According to the US Centers for Disease Control, opioids, such as heroin, oxycodone and fentanyl, were implicated in more than 47,000 deaths from overdose in 2017.

These drugs all bind to the mu opioid receptor (MOR) in the brain, which is the body's natural pleasure receptor, Averick said.

"The drugs bind, turn on the receptor and stimulate a euphoric feeling. The synthetic opioids, such as fentanyl, turn this on really, really well," he said.

Researchers said their effects are long-lasting. Fentanyl, which is much stronger than morphine, another opioid, can be absorbed into fat tissue, which protects it from being metabolised right away.

It is then slowly released from this tissue, causing effects for several hours. However, naloxone, an MOR antagonist and antidote, only stays in the system for about 30 minutes to an hour.

Because of this mismatch, repeated doses are required to help the patient recover, researchers said.

However, not all patients want to undergo the entire treatment course, and they can end up succumbing to an overdose after the naloxone is metabolised.

To overcome this challenge, Averick and his colleagues developed a drug delivery system intended to ensure that a steady, sufficient dose of antagonist is delivered over 24 hours.

The researchers reacted naloxone, which has a multi-ringed chemical structure, with polylactic acid (PLA), thus creating a naloxone polymer.

They then prepared covalent nanoparticles (CNPs) by adding this polymer to a solution of polyvinyl alcohol.

The team used a variety of analytical methods to purify and analyse the resulting particles, which are 300 nanometres in diameter.

"In collaboration with the Benedict Kolber laboratory at Duquesne University, proof-of-concept research has shown that these nanoparticles can deliver sufficient naloxone in a linear time-release fashion to block morphine's analgesic effect for 24 hours," Averick noted.

"As a next step, the study will be extended to fentanyl," he said.

Although the work was performed with mice, future studies will include an animal model that more closely simulates how humans metabolise opioids, researchers said.