PEG lipids, also known as PEGylated lipids, are a class of polyethylene glycol (PEG) derivatives that are attached to a lipid moiety, such as DMG or DSPE. These lipids are extensively used in various applications due to their ability to improve circulation times for liposome encapsulated drugs and reduce non-specific uptakes. PEG lipids play a crucial role in enhancing the properties of lipid nanoparticles, contributing to particle stability by decreasing aggregation. Optimizing PEG can prolong the blood circulation time of nanoparticles by reducing kidney and mononuclear phagocyte system clearance. Furthermore, PEG lipids can be used to conjugate specific ligands to the particle for targeted delivery. The effects of PEG lipids depend on their proportions and properties, such as the PEG molar mass and lipid length.
PEG-lipid micelles, primarily conjugates of PEG and distearyl phosphatidylethanolamine (DSPE) or PEG-DSPE, have emerged as promising drug-delivery carriers, especially in addressing the shortcomings associated with new molecular entities that have suboptimal biopharmaceutical attributes. PEG lipids are particularly effective in cancer therapy, overcoming limitations of poorly soluble drugs such as non-specific biodistribution and targeting, lack of water solubility, and poor oral bioavailability. Therefore, they have been widely used in pharmaceutical lipid nanoparticle (LNP) formulations for medications like anti-cancer drugs (e.g., doxorubicin, irinotecan, and cisplatin) and small-interfering RNA patisiran, as well as in the messenger RNA vaccines developed by BioNTech/Pfizer and Moderna.
The modification of PEGylated pharmaceuticals is a common approach to reduce clearance by the reticuloendothelial system, extend circulation time, improve pharmacokinetics, and enhance drug efficacy. However, studies have reported unexpected immune responses against PEGylated nanocarriers, including hypersensitivity reactions and anaphylaxis.
The catalog of PEG lipids includes a variety of products, such as DSPE-PEG-Cy5, DSPE-PEG-FITC, DSPE-Amide-PEG-Rhodamine, DSPE-PEG-Rhodamine, DSPE-PEG-Fluor, and many others, each with specific molecular weights and purities, indicating their diverse applications in scientific and medical research.