A New Method for Optimized Polyethylene Glycol (PEG)

Polyethylene glycol is a high molecular polymer with good water solubility and compatibility with many organic components. It has excellent lubricity, moisture retention, dispersibility, and adhesion and can be used as an antistatic agent and softener. It is widely used in cosmetics, pharmaceuticals, and other industries. In drug development research, in order to increase the half-life of protein or peptide drugs in vivo, reduce immunogenicity, and increase the water solubility of drugs, activated polyethylene glycol is chemically coupled to proteins, peptides, small molecule organic drugs, and liposomes, this is also known as PEGylation of drugs, i.e., PEGylation. Compared with non-PEGylated proteins, PEGylated proteins show significant advantages in terms of non-toxicity, low immunogenicity, high solubility, and solution mobility. PEGylation can also mask target protein drugs in the host immune system. The established therapeutic value and enormous flexibility of PEGylation make it an advanced approach for highly effective drug development.

However, PEG also gradually exposed some drawbacks. Since PEG is a non-biodegradable material, recent studies have shown that long-term use of PEG can lead to vacuolization caused by accumulation in specific organ cells. And research data show that cavitation is reversible if given enough recovery time. Therefore, how alleviating the vacuolization induced by PEG accumulation has attracted the attention of researchers. It was found that PEG-related vacuolation was more frequently observed at PEG molecular weights ≥30-kDa. Recently, researchers have developed a new method to reduce PEG accumulation in vivo, thereby alleviating vacuolization. This optimization method is based on the enzyme in the lysosome; larger PEG molecules can be gradually degraded into smaller PEG molecules in lysosomes after functioning to reduce accumulation. And the optimized PEG of this method does not affect the property, such as immunogenicity, and does not cause other adverse effects on the body. This new method ameliorated the defects in the drug treatment process and showed great potential in drug development.

The Advantages of this platform include:

• Reduced vacuolation caused by the accumulation of PEG
• No toxicity to the body
• It does not affect the efficacy of the drug

Potential Applications

• Drug development
• Optimized method of drug discovery
• Improve the safety of PEG

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Reference

1. Veronese FM, Pasut G. PEGylation, successful approach to drug delivery. Drug Discov Today. 2005 Nov 1;10(21):1451-8. DOI: 10.1016/S1359-6446(05)03575-0.