PEGylation

[1][2][3][4] PEGylation affects the resulting derivatives or aggregates interactions, which typically slows down their coalescence and degradation as well as elimination in vivo.

[7] PEGylation is the process of attaching the strands of the polymer PEG to molecules, most typically peptides, proteins, and antibody fragments, that can improve the safety and efficiency of many therapeutics.

PEGylation, by increasing the molecular weight of a molecule, can impart several significant pharmacological advantages over the unmodified form, such as improved drug solubility, reduced dosage frequency with potentially reduced toxicity and without diminished efficacy, extended circulating life, increased drug stability, and enhanced protection from proteolytic degradation; PEGylated forms may also be eligible for patent protection.

ADAGEN (pegademase bovine) manufactured by Enzon Pharmaceuticals, Inc., US was the first PEGylated protein approved by the U.S. Food and Drug Administration (FDA) in March 1990, to enter the market.

It is used to treat a form of severe combined immunodeficiency syndrome (ADA-SCID), as an alternative to bone marrow transplantation and enzyme replacement by gene therapy.

Since the introduction of ADAGEN, a large number of PEGylated protein and peptide pharmaceuticals have followed and many others are under clinical trial or under development stages.

Preferred end groups for heterobifunctional PEGs are maleimide, vinyl sulfones, pyridyl disulfide, amine, carboxylic acids and NHS esters.

[35][36][37] Third-generation pegylation agents, where the polymer has been branched, Y-shaped or comb-shaped are available and show reduced viscosity and lack of organ accumulation.

[43] To overcome the above-mentioned limitations different strategies such as changing the size (Mw), the number, the location and the type of linkage of PEG molecule were offered by several researchers.