Small solutions to big problems in drug discovery and delivery

Ijeoma Uchegbu, Professor of Pharmaceutical Nanoscience at UCL and co-founder and CSO of Nanomerics gave one of this year's keynote presentations at ELRIG Drug Discovery 2024 in London. ELRIG Drug Discovery is Europe's largest conference for the drug discovery community, offering attendees the opportunity to meet the thought leaders and industry leaders at the forefront of drug discovery. In her address, Ijeoma Uchegbu presented how nanoparticles can be used to improve medication adherence and introduced a novel, non-addictive painkiller that has the potential to alleviate the opioid crisis.

Why do patients not take their medications and why is this a problem for people working in drug discovery and delivery?

Research shows that patients with chronic illnesses often do not take their medications as prescribed. They may miss doses or stop taking them altogether. In the USA, financial reasons are a big issue. There is also the problem of side effects. These are not life or lifestyle limiting, but they are inconvenient and inconvenient. For example, someone who has had a stroke and is likely to have a second stroke might stop taking medications because of nausea or stomach upset, increasing their risk of stroke. Therefore, side effects that seem mild can actually have a big impact.

There is also a group of patients who do not believe in medication. Social scientists and pharmacists can educate them, but if their resistance is based on something pharmacological, counseling may not change compliance. Sometimes a drug hits a receptor in an unintended location and causes side effects. If we can direct the drug away from these tissues, we have a chance of reducing these effects.

What impact do nanoparticles and nanomedicine have on the problem of people not taking their medications?

Let's take eye drops as an example. We have shown preclinically that we can deliver them to the retina. If a patient is given injections in the eye, he may try to skip one of them, causing his condition to worsen. Although eye drops are not easy, they are still easier than injections. So if patients can use eye drops at home, they are more likely to take their medications.

For example, eye drops can cause certain medications to enter the blood, which can cause side effects. With our nanoparticles, the majority of the drug gets into the tissue and we cannot detect it in the blood. Through this control we can lower the dose and reduce side effects.

How did the leucine enkephalin molecule inspire the development of Envelta, a non-addictive painkiller?

Leucine enkephalin is released during painful stimuli and has a short half-life, allowing it to be released quickly. These molecules were discovered in the 1970s. Researchers tried to make them into drugs, but when injected they didn't reach the brain well and were broken down quickly. By using the enkephalin gene, which produces proenkephalin and then enkephalin, researchers found that it can provide pain relief, particularly in patients who did not respond to morphine. We have shown that we can deliver enkephalin to the brain via the nose-to-brain route, making it a suitable candidate for Envelta.

From a small molecule to solving the big problem of the opioid crisis, what do you hope to achieve with this treatment?

The opioid crisis, particularly in the United States but increasing worldwide, is a major problem. The supply of opioid medications was not always controlled, leading to widespread addiction. Although opioids are effective painkillers, they have side effects such as constipation, euphoria, and respiratory depression. We hypothesized that enkephalin, a molecule naturally secreted in the brain, could provide pain relief without these side effects. Animal studies have not shown reward-seeking behavior, giving us hope that it does not produce euphoria in humans, and these specific receptors appear to be less of a problem in respiratory depression.

We are working on one formulation while our licensor is developing another. You have made it and are now filling the delivery devices.

What have you learned about drug discovery and delivery at this stage?

Expanding production was a great learning experience. Moving from milligrams to kilograms is not just about scaling containers and solvents, but also waste management, space limitations and other logistical considerations. It took us about two years to grow from 500 milligrams to 100 grams and another year and a half to reach kilogram production.

In your talk, you emphasized the connection between discovery and delivery. How important is it for those involved to be considerate of one another?

It's crucial. Drug delivery scientists are focused on making difficult-to-deliver molecules accessible. Scientists in drug discovery often adjust the chemistry of a molecule to improve solubility or permeability. However, working with drug delivery experts could help find packaging solutions without changing chemistry.

They have highlighted the versatility of nanomedicine in diseases such as cancer and neurological diseases. What do you hope for the future of this area?

The pandemic brought nanoparticles into focus in vaccine delivery. Nanotechnology in drug delivery has been around since the late 1970s, but has only recently gained greater attention. Now researchers are considering nanoparticles for a broader range of therapeutics, which is fantastic.

About Ijeoma Uchegbu

Ijeoma Uchegbu is Professor of Pharmaceutical Nanoscience at UCL, Member of the Academy of Medical Sciences, Honorary Fellow of the Royal Society of Chemistry, Governor of the Wellcomemboard and Co-Founder and CSO of Nanomerics. She will also take up the position of President of Wolfson College, University of Cambridge later this year. Prof Uchegbu was Chair of the Academy of Pharmaceutical Sciences, Scientific Secretary of the Controlled Release Society and UCL Provost's Envoy for Racial Equality. Her groundbreaking work on the mechanisms of drug delivery led to the discovery of transformative peptide nanoparticles that can be transported across the blood-brain barrier, the enkephalin painkiller candidate Envelta™. She has received various awards for her work and is listed in Bloomsbury Publishing's Who's Who 2024.