PEGilación

Pegilación, also known as PEGylation, is a biochemical technique that involves covalently attaching chains of polyethylene glycol (PEG) to macromolecules such as proteins, peptides, enzymes, or small‑molecule drugs. The modification is achieved through various chemistries, most commonly using activated PEG derivatives that react with amino, sulfhydryl, or carboxyl groups on the target molecule. The resulting PEG‑conjugates exhibit altered physicochemical and pharmacokinetic properties while preserving biological activity.

The primary effects of pegilación include increased solubility in aqueous media, reduced immunogenicity, and shielding of the conjugated molecule from proteolytic enzymes. By enlarging the hydrodynamic radius, PEG chains impede rapid renal clearance, thereby extending plasma half‑life and allowing less frequent dosing. These advantages have driven the incorporation of pegilación into a wide range of therapeutic agents, notably interferon‑α, adalimumab, and various antibody‑drug conjugates.

Beyond pharmaceuticals, pegilación is employed in diagnostic imaging agents, biotechnological reagents, and as a tool to modulate surface properties of biomaterials. The technique also enables the creation of “stealth” nanoparticles that evade detection by the reticuloendothelial system, facilitating targeted drug delivery.

Despite its benefits, pegilación presents challenges. Heterogeneous PEG attachment can produce mixtures of isomers, complicating characterization and regulatory approval. In some patients, anti‑PEG antibodies have been reported, potentially reducing efficacy. Ongoing research explores alternatives such as site‑specific conjugation methods, biodegradable polymers, and PEG analogues to address these concerns while preserving the therapeutic gains of pegilación.