Abstract: Pegylation is the process of attaching one or more chain of PEG to a protein molecule, thus creating PEG-conjugated protein. Pegylation may be an effective method of delivering therapeutic protein and modifying their pharmacokinetics properties, in turn modifying pharmacodynamics, via a mechanism, depending on altered binding properties of native protein. Pegylation reduces renal clearances and, for some products, results in a more sustained absorption after subcutaneous administration as well as restricted distribution. These pharmacokinetic changes may result in more constant and sustained plasma concentration, which can lead to increases in clinical effectiveness which are concentration dependent. The use of liposomal carriers and modification of therapeutic molecules through the attachment of PEG moieties (Pegylation) are the most common approaches for enhancing the delivery of parenteral agents. In pegylation technology, maintaining drug concentration at. or near a target concentration for an extended period of time is often clinically advantageous, and is particularly useful in antiviral therapy.
Pegylation was first developed by Davis, Abuchowski and colleagues in the 1970s. Dr. Abuchowski coined the term “Pegylation” to describe the chemical attachment of PEG to protein and the field of Pegnology was born. Pegylation must be clearly distinguished from traditional drug formulation since pegylation modifies the structure, physico-chemical and pharmacological properties of drugs and results in a new drug molecule. Thus pegylation has to be considered at an early stage in the development process for a biopharmaceutical. For the coupling of PEG reagents to a biopharmaceutical, a large variety of reaction chemistries is available. In most cases the functional group of natural amino acids of the protein will be addressed by coupling chemistry.