N-tetradecyl-pSar25
N-tetradecyl polysarcosine-25
Polymeric lipids such as PEGylated lipids have long been used in the pharmaceutical industry as stealth coating agents. PEGylated lipids, when formulated into LNPs, have improved their circulation times and particle pharmacokinetics. As powerful as PEGylated lipids are at improving these characteristics, they also have some drawbacks- possible decreased transfection potency and production of anti-PEG antibodies. With this in mind, there has been an increased focus on PEGylated lipid alternatives.
One promising alternative to PEGylated lipids is a polypeptoid-lipid conjugate based on the amino acid sarcosine (pSar). pSar lipids of varying polymeric chain lengths have been used to tune physical properties of LNPs such as particle size, morphology, and internal structure. pSar LNPs have also proven to be an excellent mRNA transfection agent. Comparing pSar LNPs to PEGylated LNPs showed a more robust mRNA transfection potency while also improving the safety profile (Nogueira, S. et al., 2020).