N-TETAMINE-pSar35

N,N-ditetradecylamine-N-succinyl[methyl(polysarcosine)35]

Polymeric lipids have long been used in the pharmaceutical industry as stealth coating agents, most notably PEGylated lipids. When formulated into lipid nanoparticles (LNPs), PEGylated lipids have shown improved circulation times and particle pharmacokinetics. However, there are a few drawbacks associated with PEGylated lipids - they may lead to a decrease in transfection potency and the production of anti-PEG antibodies following repeated administration. Alternatives to PEGylated lipids in mRNA delivery vehicles have been investigated due to these drawbacks.

Polypeptoid-lipid conjugates based on the amino acid sarcosine (pSar) have become a promising alternative to PEGylated lipids. When formulating LNPs, pSar lipids of varying polymeric chain lengths have been used to tune physical properties such as particle size, morphology, and internal structure. Not only are they used to alter physical characteristics of LNPs, but pSar LNPs have also proven to be an excellent mRNA transfection agent. Comparing pSar lipid to PEGylated lipid LNP formulations showed a more robust mRNA transfection potency while also improving the safety profile (Nogueira, S. et al., 2020).

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• Structure

Sara S. Nogueira, Anne Schlegel, Konrad Maxeiner, Benjamin Weber, Matthias Barz, Martin A. Schroer, Clement E. Blanchet, Dmitri I. Svergun, Srinivas Ramishetti, Dan Peer, Peter Langguth, Ugur Sahin, and Heinrich Haas. ACS Applied Nano Materials 2020 3 (11), 10634-10645. DOI: 10.1021/acsanm.0c01834