PEGylation of Lipids

PEG lipids, also known as pegylated lipids, are a class of PEG derivatives attached to lipid moieties such as DMG or DSPE. Pegylation is a well-established strategy for increasing the target specificity, circulation time, and stability of lipids, thereby enhancing their use in drug development and drug delivery. BOC Sciences is committed to providing comprehensive PEGylated lipid support services to facilitate your drug delivery, gene delivery and tissue engineering programs.

What are PEG-Lipid Conjugates?

Lipid molecules consist of a hydrophilic head and a hydrophobic tail, and in the presence of an aqueous medium, lipids self-assemble to form liposomes. The presence of a hydrophilic aqueous core and hydrophobic lipid bilayer regions enables them to encapsulate both hydrophobic and hydrophilic molecules, making them ideal candidates for vaccine and drug delivery as compared to metallopolymer and dendrimer-based carriers. ideal candidate. PEG (Polyethylene glycol) is more popular due to its non-ionic, biocompatibility, hydrophilicity, and easy synthesis. PEGylated lipids consist of PEG chains, linkers, and hydrophobic anchors. One of the ends of the PEG chains in PEGylated lipids is attached to the hydrophobic anchor by a linker.

Brief Strategies for Lipid PEGylation

PEGylation of lipids involves the incorporation of PEG-conjugated phospholipids into the liposome bilayer or the grafting of PEG using functionalized lipids containing primary amino, epoxy, or diacylglycerol moieties. PEG-conjugated phospholipids can be synthesized by using PEG derivatives reactive towards the primary amines of phosphatidylethanolamine (PE). PEGylated liposomes are simply prepared by mixing these PEG-conjugated lipids in the lipid mixture during liposome preparation or incubation with preformed liposomes. In an alternative approach, lipophilic compounds bearing reactive groups such as amino and carboxyl groups can also be used to create PEGylation sites on the liposome surface. By incorporating these components into the bilayer, 500-2,000 reactive functional groups can be introduced for reaction with various PEGylation reagents.

Fig. 1. Regimes in a PEG coated liposome a) Interdigitated Mushroom; b) Mushroom Regime; c) Brush Regime (International Journal of Lipids. 2020, 1(2): 1-20).

PEG is often covalently bound to lipid molecules and mixed with other lipids to form lipid-based nanoparticles. The chain mobility of PEG molecules can provide hydration during circulation and avoid non-specific adsorption of components in tissues and body fluids. This approach helps the nanoparticles prolong their circulation and avoid absorption by the reticuloendothelial system, allowing them to travel safely through the body. Furthermore, the density of PEG on the surface of lipid-based nanoparticles is critical for the design of these nanocarriers. As the density of PEG-grafted on the liposome surface increased, the half-life also increased, which was attributed to non-specific uptake of proteins and decreased uptake by the reticuloendothelial system. The low incorporation of PEG does not fully protect the nanoparticles from interacting with serum proteins because PEG does not provide the desired steric stability to the nanoparticles. Therefore, for mechanical stability reasons, the proportion of PEG in lipid bilayers is usually lower than 5-6%.

Our Lipid PEGylation Capabilities

BOC Sciences can provide a variety of PEG-modified liposome derivatives with different molecular weights and functional groups. The molecular weight of our commonly used PEG is from 600-12000, including the most commonly used PEG from 2000 to 5000. Our PEGylated lipid capabilities include:

References

1. Misra, A. et al. PEG - A versatile conjugating ligand for drugs and drug delivery systems. Journal of Controlled Release. 2014, 192: 67-81.
2. Kalyanram, P. et al. Understanding the Stealth Properties of PEGylated lipids: A Mini-Review. International Journal of Lipids. 2020, 1(2): 1-20.