Pegylated

PEGylated refers to a molecule that has one or more chains of polyethylene glycol (PEG) covalently attached. PEGylation is a bioconjugation technique used to improve the pharmacokinetic and biophysical properties of therapeutic proteins, peptides, enzymes, and some small molecules, as well as nanoparticles and liposomes. By increasing the hydrodynamic size, PEG chains reduce renal clearance, prolong circulation time, and can shield the molecule from proteolysis and immune recognition. PEGylation can also enhance solubility and stability.

Conjugation methods vary, including random attachment to lysine residues or N-termini, or site-specific attachment using engineered residues or enzymatic methods. Common linkers and PEG sizes range from about 5 to 40 kilodaltons. Notable clinical PEGylated therapies include pegylated interferon alfa-2a (Pegasys), pegylated L-asparaginase (Pegaspargase), and pegylated liposomal doxorubicin (Doxil). The concept has also been applied to increase half-life of non-protein drugs and to form stealth liposomes.

Challenges include the development of anti-PEG antibodies in some patients, which can accelerate clearance or trigger reactions. PEGylation can also reduce biological activity due to steric hindrance, and manufacturing is more complex with potential batch heterogeneity. Despite these limitations, PEGylation remains a widely used strategy to extend systemic exposure and reduce dosing frequency in several approved therapeutics.