A new class of polymers has been used in patients for the first time. The compound is the first new drug solubilising agent in decades. Introduced in 2014 by chemist Matthias Barz from Leiden University, it offers a unique alternative to current options
Getting your molecules into patients: that is the ultimate goal. Matthias Barz, chemist at LACDR, is extremely content with this milestone in his drug delivery journey. 'When I started, people told me this would never work. Luckily, the company Lubrizol believes in these materials. And now, here we are. A phase 1 clinical trial has started.'
The polymers presented by Barz aren't drugs themselves. They're excipients: 'helper substances' that improve how a medicine works, for example by enhancing solubility or stability. While they don't directly cause a therapeutic effect themselves, excipients can influence how well a patient tolerates a drug. The most commonly used ones are hardly or not at all biodegradable and remain in the body, leading to adverse effects over time.
The new class of polymers, called polypept(o)ids, are made from body-own building blocks, amino acids. Because the body recognises them as 'self', they are better tolerated and are broken down over time. This makes them less likely to trigger immune reactions even after multiple doses.
What are polypept(o)ids?
Polypept(o)ids combine two parts: polypeptides (similar to natural proteins) and polypeptoids (more stable and less likely to provoke the immune system). A key poylpeptoid is polysarcosine, a polymer that adds "stealth" and body suitability. The chemistry isn't new, but Barz's lab was the first to produce them in a pure and controlled way-making medical applications possible.
Barz turned short peptide chains into functional polymers
Barz found a way to turn short peptide chains into longer, functional polymers. These behave like polyethylene glycol (PEG), currently the most widely used polymer in biomedicine. 'We wanted a polymer with PEG-like properties, but biodegradable into fragments, which are safe and familiar to our body,' he explains.
Eventually, Kevin Sill and Bradford Sullivan patented a version of this polymer. They tested it across various drug types and found it worked well. The rights were later acquired by Lubrizol, a mid-sized pharmaceutical company. Lubrizol developed the product further, branded it as Apisolex®, and took the leap to bring the system to patients.
'Many biodegradable materials degrade too quickly in aqueous solution. Ours stay stable.'
Polypept(o)ids are worth the risk
This is a rare achievement. Barz notes that no new excipient has been introduced in decades. 'Pharmaceutical companies don't like taking risks for very good reasons. The drug itself might already fail-so adding a new ingredient introduces more uncertainty. Most companies stick with what's already used.' But what's already broadly used might have its downsides. It is known that PEG causes immune responses and can accumulate in liver and spleen.
But both Barz and Lubrizol believe polypept(o)ids are worth the risk. They are biodegradable and highly stable in water, which makes them ideal for liquid drug formulations or vaccines. 'Many biodegradable materials degrade too quickly in aqueous solution,' Barz says. 'Ours stay stable.'
Besides Apisolex® from Lubrizol, other companies, like Curapath, make a broad range of polypept(o)ides commercially available for fundamental research and drug development, which enables now researchers around the world to explore the potential of the polymers introduced by the Barz lab.
'People are hesitant, even when the science is solid'
Barz hopes the results of this first study in humans will be promising. In the long term, he believes regulatory agencies will demand that all injectable materials be either fully metabolised or fully excreted. That would give biodegradable excipients a big advantage.
Still, adoption will take time. 'If you say we now have something better, you're implying that older treatments, like the COVID vaccine, used something less ideal,' Barz explains. 'That makes pharmaceutical industry hesitant, even when the science is solid.'
'Never stop trying'
He hopes this breakthrough will inspire young scientists. 'Everyone said this wouldn't work. But science should always strive for innovation. You need some luck and brave partners, but never stop trying remains a necessity.'
