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N-hexadecyl-pSar25
N-Hexadecyl polysarcosine-25
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 some negatives associated with PEGylated lipids - decrease in transfection potency and production of anti-PEG antibodies. Due to these drawbacks, there has been much effort towards finding alternatives to PEGylated lipids.
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).
