Polyethylene glycol modification use and development prospects of drugs

Polyethylene glycol (PEG) is a pH-neutral, non-toxic, water-soluble hydrophilic polymer with repeating units of oxyethylene and terminal groups of two hydroxyl groups, linear or branched. Chain structure. PEG polymer is the polymer with the lowest level of protein and cell absorption in polymers. Due to its non-toxic PEG and good biocompatibility, PEG has been approved by the FDA as an injectable pharmaceutical polymer. Modification is the process of chemically coupling activated PEG to a drug, ie, PEGylation. Polyethylene glycol (PEG) was first used for drug modification. In 1977, Abuchowsk et al. used PEG to modify bovine serum albumin. It was found that it can effectively change its immunological properties. The researchers then used PEG to modify the anticancer drug asparaginase and applied it to the clinic.

In addition, the researchers have successfully applied PEG to the modification of small molecule drugs such as acyl deaminase, interferon and other protein drugs, camptothecin, paclitaxel, cytarabine, and scutellarin. The molecular weight of the drug increases beyond the molecular weight range of the kidney filtration, thereby effectively prolonging the half-life of the drug and enhancing the stability of the drug; the water solubility of the PEG-modified drug generally increases, and the drug improves the pharmacokinetics by changing the molecular structure. And the nature of the drug and the like, the blood concentration of the site of action is increased.

The PEG-modified drug has outstanding advantages compared with that before modification: (1) the solubility of the drug is improved; (2) the half-life is prolonged; (3) the maximum blood drug concentration is decreased, and the blood drug concentration is less fluctuating; (4) Reduced enzymatic degradation, reduced immunogenicity and antigenicity; (5) reduced toxicity.Clinically, protein drugs have specific action sites and clear curative effects, but they are easily hydrolyzed by proteases in the gastrointestinal tract. The half-life in plasma is short and the antigenicity is strong. The biochemical properties of proteins can be changed by PEG modification technology. Increase protein water solubility and stability.