Pegylation: engineering improved pharmaceuticals for enhanced therapy

Abstract

Conjugating biomolecules with polyethylene glycol (PEG), a process known as pegylation, is now an established method for increasing the circulating half-life of protein and liposomal pharmaceuticals. Polyethylene glycols are nontoxic water-soluble polymers that, owing to their large hydrodynamic volume, create a shield around the pegylated drug, thus protecting it from renal clearance, enzymatic degradation, and recognition by cells of the immune system. Agent-specific pegylation methods have been used in recent years to produce pegylated drugs that have biologic activity that is the same as, or greater than, that of the parent drug. These agents have distinct in vivo pharmacokinetic and pharmacodynamic properties, as exemplified by the self-regulated clearance of pegfilgrastim, the prolonged absorption half-life of pegylated interferon alpha-2a, and the altered tolerability profile of pegylated liposomal doxorubicin. Pegylated agents have dosing schedules that are more convenient and more acceptable to patients, and this can have a beneficial effect on the quality of life of patients with cancer.