PEG-Cholesterol

PEG-Cholesterol is a synthetic amphiphilic conjugate formed by covalently attaching a polyethylene glycol (PEG) polymer to a cholesterol molecule. This compound serves as a critical excipient in lipid-based nanocarriers, imparting steric stabilization, prolonged systemic circulation, and enhanced biocompatibility. The PEG moiety confers hydrophilicity and a protective hydration layer, while the cholesterol component integrates into lipid membranes, reinforcing structural integrity and facilitating self-assembly in formulations such as liposomes and lipid nanoparticles.

Chemical Structure and Mechanism of Action The conjugate typically features cholesterol (cholest-5-en-3β-ol) linked via an ester, carbamate, or ether bond to a PEG chain of varying molecular weights (commonly 1–5 kDa, e.g., mPEG2000-cholesterol). This architecture enables insertion into phospholipid bilayers through hydrophobic interactions of the sterol ring, while the extended PEG chains create a steric barrier that inhibits protein corona formation and macrophage uptake. Consequently, PEG-Cholesterol reduces immunogenicity, extends plasma residence time, and supports efficient cellular internalization via endocytosis, with potential modulation of membrane curvature and fusion properties.