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Drugs with fewer side effects through a collaboration between LACDR and PTS

LACDR, the Leiden Institute for Drug Research, developed better tolerated excipients to prevent adverse effects related to the surface of nanosized drugs such as vaccines. LADCR professor of Biopharmacy Matthias Barz and Polypeptide Therapeutic Solutions (PTS) are collaborating to develop processes enabling the large-scale production of these excipients and enable a broader application of such materials in pharmaceutical industry.

Excipients are an important part of the final drug formulation along with the active ingredient of the therapeutic. One example of an excipient are the lipids included in the mRNA vaccines against Covid-19. One in 10,000 people vaccinated against SARS-CoV-2 with the novel mRNA vaccines develop serious adverse effects such as inflamed heart muscle or pericardium. 'That's not a lot, but now that these vaccines have been used on such a large scale, it still involves too many people,' says Matthias Barz. Prof. 

Reducing undesired immune responses of mRNA medicines

Barz and his laboratory specialize in the synthesis of nanoparticles for biomedical applications and polymers based on body-own amino acids, to reduce drug-related adverse effects or enable novel active molecules to become drugs. They also make polymers in this way, long chains of molecules that help to get the active substance of a medicine where it is needed.

In collaboration with researchers from BioNTech, they made a discovery about undesired immune responses of mRNA formulations comparable to the current mRNA vaccines. In these formulations, it is common practice to add so-called polyethylene glycol (PEG) lipids as an excipient to improve their effectiveness. The side effects have been shown to decrease in mice if these lipids are replaced with lipids containing the polysarcosin polymer.  Polysarcosine is based on the natural amino acid sarcosine, which may account for the improved tolerability of this material. 

Success requires a specialized manufacturing company

The Barz laboratory synthesizes a variety of polysarcosine-based polymers that are typically combined with other polypeptides yielding polymers consisting entirely of natural amino acids. These systems can be applied as excipients or to the production of functional nanoparticles for diagnosis and therapy. 

Producing such systems at research scale is one thing, but moving towards clinical translation and large scale production is require more. 'We can manufacture our products on a laboratory scale, but in order to make them available on a large scale efficiently and safely, you have to comply with certification regulations from the European Medicines Agency EMA. PTS has extensive experience with this, specifically in the field of drug delivery systems based on polypeptides. Because of this, they are the perfect partner for us.'

Aim: improving the performance of active pharmaceutical ingredients

Through their collaboration, the LACDR and PTS aim to introduce new excipients and complete drug delivery systems that can improve the performance of active pharmaceutical ingredients, e.g., mRNA, by making such systems better tolerated. The partners will collaborate over four years on nanoparticles that can also play a role in the diagnosis and therapy of cancer, inflammation, and bacterial infections. Matthias Barz: ‘Our materials will combine advanced features of functionality, high biocompatibility, and tunable degradability and hopefully improve the performance of existing systems.

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