Vaccine Lab / Alfa Chemistry
PEG Lipids
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PEG Lipids

PEG lipids are an important component of lipid nanoparticles (LNPs). They consist of a hydrophilic molecule of PEG conjugated to a hydrophobic alkyl (or lipid) chain, where the PEG domain is attached to the LNP surface while the alkyl chain is attached to the LNP bilayer. This molecule is widely used in the field of liposomal nucleic acid delivery to provide a polymeric coating that can impart good pharmacokinetic properties to the circulating particles. Typically, these lipids are used as important components in the self-assembly of cationic and neutral lipids with polynuclear acids, forming small, stable lipid/nucleic acid complexes that exhibit a long cycle time in vivo and accumulate at disease sites.

The PEG lipids on the surface of the LNPsFigure 1. The PEG lipids on the surface of the LNPs [1]

The importance of PEG lipids for nucleic acid delivery

An important milestone for the clinical use of LNPs in the delivery of nucleic acids is the development of PEG lipids. First, PEG lipids shield the LNP surface thereby protecting them against opsonins and uptake by the mononuclear phagocyte system, as well as preventing their aggregation in the circulation. Second, PEG lipids prevent aggregation during production and storage, and their incorporation can dictate LNP size. These two functions serve to increase the overall stability of the LNP. In addition, the addition of PEG lipids to LNPs prolongs the circulation time of LNPs due to the steric barrier effect of PEG lipids. This property reduces binding of LNPs to plasma proteins, reduces rapid elimination by the reticuloendothelial system, and consequently, assists in the accumulation of the nanoparticles at disease sites.

Effect of PEG lipid properties on nucleic acid delivery

The amount of PEG lipids incorporated in LNPs should be controlled carefully and kept to a minimum. Having higher PEG contents usually increases the residence time of LNPs in the blood circulation but may prevent their fusion with the endosomal bilayer and hinder the intracellular delivery of nucleic acids. The lipid length in PEG lipids is equally important for the effectiveness of nucleic acid delivery. PEG lipids containing shorter chains (e.g., C8–14) have been found to diffuse out of the LNP more rapidly compared to the longer chains (e.g., C16–24) in the presence of a lipid sink (i.e., plasma lipoproteins). For example, 1,2-dimyristoyl-rac-glycero-3-methoxypolyethylene glycol-2000 (PEG2000-DMG) and 1,2-distearoyl-rac-glycero-3-methoxypolyethylene glycol-2000 (PEG2000-DSG) are neutral PEG lipids, and the length of their saturated alkyl chains is C14 and C18, respectively. Lipid nanoparticle-siRNA formulations containing PEG2000-DMG have shorter circulation times and higher delivery efficacy in vivo than formulations containing PEG2000-DSG. This difference may be attributed to the faster dissociation of PEG2000-DMG from lipid nanoparticles, compared with PEG2000-DSG, which may benefit cellular uptake and endosomal escape of lipid nanoparticles [2].

Structure of PEG2000-DMGFigure 2. Structure of PEG2000-DMG

What we offer

Lipid-anchored PEGs preferentially deposit on the LNPs surface, where they act as a barrier which sterically stabilizes the LNP and reduces nonspecific binding to proteins. Alfa Chemistry supplies PEG lipids to companies researching nucleic acid delivery systems. If you cannot find the PEG lipid you need, please contact us. We also offer product customization according to customer's detailed requirements.


  1. Buschmann, M. D.; et al. Nanomaterial delivery systems for mRNA vaccines. Vaccines. 2021, 9, 65.
  2. Robert, L.; et al. Lipid nanoparticles for mRNA delivery. Nature Reviews Materials. 2021, 6: 1078-1094.

Our products and services are for research use only and cannot be used for any clinical purposes.

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