Polyethylene glycol (PEG) is a well-known polymer with until-now unique physico-chemical properties that boosted its extensive application in the pharmaceutical and cosmetic industry [1]. PEG enhances solubility and biocompatibility of APIs and nanomedicines acting as shielding to reduce immunogenicity and enhance blood circulation times. PEG-lipid conjugates are commonly applied in the most successful nucleic acid delivery systems: lipid nanoparticles (LNPs) [2], with BioNTech/Pfizer and Moderna/ /NIAID mRNA COVID-19 vaccines leading the way [3,4]. However, the extensive use of PEG in marketed products has raised concerns related to immunogenicity and loss of efficiency of PEG-medicines due to the production of anti-PEG antibodies which clear them from the bloodstream (Accelerated Blood Clearance, ABC) [5] . This is aggravated by the exposure of the population to PEG by the worldwide COVID vaccination campaign pushing the need for PEG-free alternatives.<br/>For this reason, at Curapath we work with a portfolio of PEG alternatives such as polysarcosine (PSar) which has analogue solubility, and macromolecular properties than PEG, with a wide and versatile C-N terminus group functionality for conjugation [6]. PEG alternatives have been produced and scaled up in technical batches with batch-to-batch reproducibility and QC compliance. We have investigated the advantages of their use in shielding strategies for protein-delivery, small molecule encapsulations and LNPs. Our PEG alternatives have a low interaction with blood proteins, a lower immunogenic profile compared to PEG allowing to avoid the ABC phenomena. Overall, Curapath has engineered a library of different PEG alternatives with the aim to not only overcome PEG drawbacks but to confer different surface features to help build the next generation LNPs.

Industrially feasible PEG alternatives based on bioinspired polymers with shielding properties

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