LipidPEG

LipidPEG, short for lipid-polyethylene glycol conjugate, is a class of amphiphilic molecules produced by covalently attaching polyethylene glycol (PEG) chains to the hydrophobic tail of a lipid. This modification bestows the lipid with a hydrophilic corona, enabling it to form stable nanostructures such as liposomes, lipid nanoparticles (LNPs), and micelles in aqueous solutions. The synthesis typically involves coupling reactions between a functionalized PEG (often amine- or hydroxyl-terminated) and a lipid precursor bearing a reactive group, such as a maleimide, NHS ester, or activated fatty acid, under controlled reaction conditions.

The primary application of LipidPEGs is in drug delivery. By incorporating LipidPEG into the surface of liposomal or lipid‐based carriers, the particles acquire a "stealth" property that reduces protein adsorption (opsonization) and subsequent clearance by the mononuclear phagocyte system. This results in prolonged systemic circulation times and improved biodistribution. LipidPEGs are a key component of the lipid‑nanoparticle formulations used for messenger RNA vaccines, where they help maintain particle integrity and reduce immunogenicity of the carrier. Additionally, LipidPEGs are employed in gene therapy vectors, oral drug carriers, and imaging agents.

Advantages of LipidPEGs include tunable PEG chain length (commonly ranging from 2 to 20 kDa) to control surface hydration layers, ease of large‑scale synthesis, and chemical stability. However, concerns such as the potential for anti‑PEG antibody development and PEGylation‑induced reduction in cellular uptake at high densities remain subjects of ongoing research. Regulatory agencies monitor these factors in the approval of PEGylated therapeutics.