Nanoparticle-Delivered Pain Medication Could Help Address the Opioid Crisis
Nanoparticle technology could help deliver pain medications to the brain and reduce harmful side effects.
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The opioid crisis, whilst predominantly associated with the United States, has become a growing global health issue. In the wake of this epidemic, drug developers have been searching tirelessly for non-addictive medicines that can combat pain without triggering the brain’s reward systems that contribute to the risk of addiction.
Recent success has seen the US Food and Drug Administration (FDA) announce the approval of Journavx™ (suzetrigine), the first new class of pain management medicine to be approved in the US since 1998. Further breakthroughs in non-addictive pain medications may come in the form of therapeutics that utilize a nanoparticle delivery system.
Dame Ijeoma Uchegbu, professor of pharmaceutical nanoscience at University College London, president of Wolfson College at the University of Cambridge and co-founder and CSO of Nanomerics, was the first to demonstrate peptide transport into the brain, using peptide nanoparticles delivered via the nose-to-brain route. This research led to the development of the pain medicine candidate Envelta™ (leucine-enkephalin), which is expected to enter Phase 1 clinical trials in the near future.
The drug was inspired by the molecule leucine-enkephalin, which researchers found could provide pain relief, especially in patients who didn’t respond to morphine. Drug developers believed that leucine-enkephalin, a molecule naturally secreted in the brain, could provide pain relief without side effects seen in other opioids such as euphoria.
However, when researchers tried to use the molecule therapeutically, they found it degraded quickly and couldn’t reach the brain. Envelta is designed to overcome this challenge by utilizing a patented intranasal nanoparticle-based drug delivery system to bypass the blood-brain barrier.
Technology Networks caught up with Uchegbu to learn more about the nanoparticle delivery system behind Envelta and how this platform could help overcome issues surrounding efficacy and off-target effects.
Can you tell us more about the nanoparticles you have designed for drug delivery?
Ijeoma Uchegbu, PhD, DBE (IU):
Drug developers have been working with nanoparticles for a few decades and our nanoparticles are a bit different from those that are more well-known. Traditional nanoparticles are made of lipids, which means they are made of small molecules clustered together to make a particle. The way I like to think about that is to imagine a ball of wool, which is made from tiny strands of wool all held together. Our nanoparticles are slightly different in that the strands are very long, so they can curl around and tangle up. Immediately you know that if a ball of wool is made of small fibers it's going to break up more easily, than if it's made of longer fibers. This analogy is something that I was able to build into these nanoparticles when I was trying to understand stability very early on.
What makes our nanoparticle technology very useful is that they’re very good at controlling where a drug goes in the body. One example is the ability to deliver therapies to the brain through the nose. What we’re talking about here is the ability to shunt the drug molecules to the area of disease and away from healthy tissue. This means delivering molecules to the brain but not much entering the blood, which as part of the body’s transport network could result in the drug reaching healthy tissues and cells.
BF:
IU:
Taking the eye as an example, when you add an eye drop to your eye it sits in that little pocket at the bottom of your eyelid for just two minutes. In those two minutes, the drug must move out of the water droplet into your tear film, through your mucosa and into your tissues. This is a very short time for all that to happen, so what you observe is that, often, the drug doesn’t go anywhere and it drains.
With the nanoparticles, they stick to the surface of the eyeball due to charge interactions. Not only do they stick, but conveniently, when they stick, they are damaged. When damaged the drug falls out of the particle and goes into the tissue. That way you have more of the drug going into the desired tissue in the eye, less of it draining, because it’s stuck, and even when it drains, it's still in its nanoparticle so less of it goes to the blood and therefore to healthy tissues.
We’ve tested the polymers that make up the nanoparticle and they don't damage cells. Some of the lipid-based delivery systems, because of their very nature, aren’t very friendly to cells, but these kinds of particles are more friendly to cells and so more biocompatible.
We’ve done the tests in our lab where we looked at lipids that are used to deliver nucleic acids and compared these to our own nanoparticles and observed that they can be up to 10 times less toxic to cells.
Quite recently we have also done some human trials on the eye drops made of our nanoparticles and, although the trial has not yet released the topline data, we know that after dosing was complete the nanoparticles do not irritate the eye and are well tolerated.
BF:
IU:
The molecule itself, on the face of it, wasn't a great target because it has some elements of water solubility. However, because Envelta is made of amino acids that are water soluble and amino acids that are not water soluble, it has amphiphilic character. So, it's compatible with water and compatible with some organic solvents. The amphiphilic character allows us to encapsulate leucine-enkephalin within the nanoparticles.
When deciding on a molecule we were also struck by the fact that leucine-enkephalin rapidly degraded. When we put the molecule in nanoparticles, we measured the degradation and it slowed it down as it was no longer immediately available to the enzymes.
We use the nose-to-brain route to deliver the drug to the brain. Our goal was to get the drug to the olfactory region because there you have the olfactory epithelium and neurons as a gateway to the brain. Within your nose, you've got enzymes that can break things down. However, we found that when we wrap enkephalin in these nanoparticles, it's less likely to degrade. This allows the molecule to bypass the blood-brain barrier, get into the brain and show efficacy.
