N-TETAMINE-pSar25 A88146 (Previously 880146) N,N-ditetradecyl-polysarcosine-25

Polymeric lipids such as PEGylated lipids have long been used in the pharmaceutical industry as stealth coating agents. When formulated into lipid nanoparticles (LNPs), PEGylated lipids often improve their circulation times and particle pharmacokinetics. PEGylated lipids do come with a few drawbacks - they may lead to a decrease in transfection potency and the production of anti-PEG antibodies following repeated administration. With these drawbacks in mind, alternatives to PEGylated lipids in mRNA delivery vehicles have been investigated.

Polysarcosine (pSar, a polypeptoid based on the amino acid sarcosine) lipids have become a promising alternative to PEGylated lipids. When formulating LNPs, pSar lipids of varying polymeric chain lengths have been used to tune physiochemical properties such as particle size, morphology, and internal structure. Aside from being able to change the physical nature of the LNP, pSar LNPs have also proven to be an excellent mRNA transfection agent. When compared to similar LNPs formulated with PEGylated lipids, LNPs formulated with pSar lipids exhibited a more robust mRNA transfection potency while also showing an improved safety profile (Nogueira, S. et al., 2020).