PEGylation Technologies for Better Protein Drugs

Dong Hee Na, Ph.D.

College of Pharmacy, Chung-Ang University

(E-mail: dhna@cau.ac.kr)

PEGylation is a pharmaceutical technology that attaches one or more polyethylene glycol (PEG) molecules to therapeutic molecules, thereby improving their pharmaceutical properties. PEG, a synthetic polymer comprised of repeating ethylene oxide units, is chemically inert and has low toxicity, and has been approved by Food and Drug Administration (FDA) for oral, intravenous, and dermal applications in the pharmaceutical industry. The attachment of PEG to proteins affords the prolonged circulation lifetime owing to reduced renal clearance, improved stability against proteolytic enzymes, enhanced solubility in biological fluids, and reduced toxicity/immunogenicity. Since the first PEGylated enzyme products (PEG-adenosine deaminase; Adagen^® and PEG-L-asparaginase; Oncaspar^®) appeared on the market in the early 1990s, over 18 PEGylated products have been approved and launched. The approved PEGylated products include various classes of drug molecules, such as enzymes (adenosine deaminase, asparaginase, uricase, and phenylalanine ammonia lyase), interferons (interferon α-2a, interferon α-2b, and interferon beta-1a), granulocyte colony-stimulating factors, hormones (epoetin-β), antibody fragments (anti-TNF Fab), coagulation factors, oligonucleotide aptamers, synthetic peptides, and small organic molecules (naloxone). These approved drug products have demonstrated the applicability and effectiveness of PEGylation technology. This presentation overviews advances of PEGylation technology and then introduces strategies for precise PEGylation and non-covalent PEGylation approaches for protein formulation development.