Protein, peptide and non-peptide drug PEGylation for therapeutical application: a review

For many years proteins have been investigated as therapeutic agents, but unfortunately their potential advantages could not be exploited completely. The main drawbacks regard the intrinsic short life in the body, the immunological adverse reaction and the proteolytic digestion. Among all the approaches studied for overcoming these problems, PEGylation (the modification of molecules with polyethylene-glycol, PEG) achieved the most interesting results leading to a novel series of products that reached already the market and, furthermore, promising others will be available soon. Since the first studies in this field, the conjugation of PEG to a protein showed the possibility to improve the pharmacokinetics profile of linked drug. In the last years this technology, firstly developed for proteins, has been transferred to non-peptide drugs, opening a new area of investigation that is now receiving increasing interest. This leads to new opportunities for many therapeutic treatments since it is possible to use molecules that could not be used before for limitations such as inadequate water solubility, high non-specific toxicity and poor pharmacokinetic profiles. In this review the recent achievements in PEGylation of protein, peptide and non-peptide drugs were described for what the chemistry of binding is concerned, and many examples from literature are reported both in the field of protein therapeutic as well as non-peptide drugs.