PEGlipids

PEGlipids, short for polyethylene glycol–lipids, are lipids that are covalently bound to polyethylene glycol (PEG) chains. They typically consist of a lipid anchor, such as DSPE or DPPE, linked to a PEG chain of defined length (for example PEG2000 or PEG5000). This combination allows the molecule to insert into lipid-based assemblies while presenting the PEG chain to the surrounding aqueous environment.

In lipid-based nanoparticles, including liposomes and lipid nanoparticles used for nucleic acid delivery, the PEG moiety forms a hydrated steric barrier on the particle surface. This barrier reduces protein adsorption and recognition by the mononuclear phagocyte system, thereby lowering clearance and extending circulation time. PEGlipids can also serve as spacers to attach targeting ligands or cargo to the particle surface, enabling functionalization without extensive disruption of the lipid matrix.

Common examples include DSPE-PEG2000 and other PEGylated phospholipids such as mPEG-DSPE. These components are widely used to decorate lipid bilayers and to tune properties such as particle size, stability, and release kinetics. Applications encompass stealth liposomes for drug delivery and lipid nanoparticles for delivering nucleic acids and related therapeutics, where PEGylation helps to improve pharmacokinetics and biodistribution.

Limitations and considerations include the potential for anti-PEG antibodies in some individuals, which can cause accelerated blood clearance or hypersensitivity reactions. PEG chain length, density on the particle surface, and compatibility with other formulation components must be carefully optimized. Proper manufacturing controls are required to ensure batch-to-batch consistency.