PEGylation for improving the effectiveness of therapeutic biomolecules.

Proteins have gained an important role in clinical practice, and they are the treatment of choice or even the only therapy for several pathologies. Unfortunately, their great potential is often hampered by relevant shortcomings such as immunogenicity and fast body clearance. Polymer conjugation, especially with polyethylene glycol (PEG), has emerged as a suitable drug delivery solution to address these drawbacks. Furthermore, this technology has been found to be a powerful approach to increase the general therapeutic efficacy of biomolecules. After the first PEG-protein derivatives were released, it was clear that a wider exploitation of PEGylation could be reached only through thorough development of the methods of conjugation. At the moment, different PEG coupling strategies and PEG polymers are available. The research in this field is very active and a large effort has been focused on developing releasable PEGs, which are polymers able to release the conjugated protein. This feature enables the recovery of the protein activity that is commonly reduced after polymer coupling.