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Monodisperse PEGs for Therapeutics

In the world of therapeutics, several challenges have hindered the development and overall success of drugs and vaccines. One pressing issue is the short half-life of therapeutics, with drugs rapidly breaking down and being eliminated from the body. This leads to poor drug efficacy and consequently having to introduce frequent dosing and potential issues with patient compliance. Additionally, some drugs face problems with solubility, making it difficult for poorly soluble compounds to be effectively absorbed. Maintaining drug stability during storage and administration is also crucial as many compounds, in particular biologics, tend to degrade or undergo chemical changes. Addressing these problems is essential for optimal therapeutic outcomes and clinical approval.1 One strategy for increasing the stability of drugs before and after administration, as well as increasing water solubility, is to chemically incorporate inert polyethylene glycol (PEG) into the drugs. This process has been critical in new drug discovery as well as in generating new therapeutics from previously known drugs.

PEGylation is a bioconjugation technique, which involves attaching PEG chains to therapeutic agents, such as drugs or vaccines. This process enhances the pharmacokinetic and pharmacodynamic properties of the molecules, leading to prolonged circulation time in the body, better solubility, and improved stability. PEGylation has been a successful strategy for new drug development in many instances but until now it has been performed with commercially available off-the-shelf chemicals that are composed of polymers with non-uniform chain length, known as polydisperse PEGs.2

Over the last 25 years, Polypure has developed techniques to synthesise and purify PEGs to a distinct chain length, known as monodisperse, uniform, or single-length PEGs. These high-quality PEGs lead to higher reproducibility in production, a thorough understanding of reaction dynamics, and grant greater efficiency in the purification and analysis of products. The nature of Polypure’s PEG derivatives facilitates quality control, and simplifies monitoring, and optimisation of the chemical processes.

Many companies are starting to choose uniform PEG alternatives for their product development and manufacturing. The consistency of raw materials contributes to reliable production, it increases reproducibility and dramatically reduces batch-to-batch variations. This not only favours high-quality final products but also streamlines research and development activities by reducing the consecutive complex impurity profile associated with polydisperse materials. Ultimately, the use of monodisperse PEGs contributes to more precise and reliable outcomes for pharmaceutical manufacturing.

R&D projects

Polypure is actively engaged in two projects that center around

PEGylation, both of which are supported by the European Union’s Horizon 2020 Research and Innovation Programme through the Marie Skłodowska-Curie Actions. Polypure’s role is to provide tailor-made PEG derivatives and to purify compounds from complex mixtures.

The NOVA-MRI (MSCA Grant #859908) project aims to improve the stability of PLGA nanoparticles for the development of novel 19F MRI contrast agents. This is achieved by attaching monodisperse PEG derivatives onto fluorine-labelled nanoparticles. Polypure is actively investigating the impact of PEG length and the choice of end-group on the binding of nanoparticles to various types of immune cells for improved biocompatibility.

The success of the SARS-CoV-2 mRNA vaccine has showcased the substantial contribution that PEGs can make in advancing vaccine development. The PAVE project (MSCA Grant #861190) seeks to establish immunotherapy-driven strategies for the treatment of pancreatic cancer. Polypure’s responsibility in the PAVE network is to develop PEG products that can be used for vaccine technologies such as lipid nanoparticles (LNPs) and peptide-based vaccines.

PEG-peptides

Peptide-based cancer vaccines are made up of sequences of amino acids derived from tumor antigens (Figure 1). These peptide sequences are typically lengthy and comprise blocks of hydrophobic amino acids, making the synthesis difficult and requiring rigorous purification to obtain a high-quality product.3 The contribution of Polypure is to assist in PEGylating peptides to improve solubility and simplify downstream processing of vaccine. We have shown that the incorporation of PEG chains in peptide sequences reduces synthesis, purification, and solubility problems frequently encountered with hydrophobic peptides.

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