PEGlipidens

PEGlipidens are a class of amphiphilic molecules composed of a lipid moiety covalently attached to a poly(ethylene glycol) (PEG) chain. Also referred to as PEGylated lipids, they are widely used to modify the surface properties of lipid-based nanomaterials, including liposomes, micelles, and lipid nanoparticles.

The lipid tail provides the hydrophobic anchor, while the PEG chain creates a hydrophilic corona that reduces protein adsorption and recognition by the immune system. Common lipid anchors include DSPE, DPPE, and other phospholipid or cholesterol derivatives, linked to PEG chains of varying length (from about 1000 Da to 5000 Da or higher). Linkages include amide, carbamate, or ester bonds.

In formulation, PEGlipidens are incorporated into lipid bilayers or assembled into micelles or lipid nanoparticles during preparation. Their presence can stabilize particles, control size, and extend circulation time by forming a stealth layer. They also offer a convenient handle for attaching targeting ligands or imaging moieties at the distal end of the PEG chain.

Applications include stealth liposomes for drug delivery, lipid nanoparticles for nucleic acids, and other nanomedicine platforms. Pegylation reduces opsonization and clearance by the mononuclear phagocyte system, but can also hinder cellular uptake. In some individuals, anti-PEG antibodies may reduce efficacy or cause hypersensitivity.

Synthesis and commercial availability: PEGlipidens are typically synthesized by coupling PEG chains to preformed lipid molecules or by synthesizing PEG-lipids with headgroups compatible with liposomal formulations. They are commercially available in various PEG lengths and lipid anchors.