Polyethylene Glycol Chemistry in Biomedical Applications

Polyethylene glycol (PEG) is a linear polyether renowned for its biocompatibility, hydrophilicity and low immunogenicity, making it a cornerstone of modern drug delivery and therapeutic strategies. Through covalent attachment to drugs, peptides and nanoparticles, PEG enhances solubility, reduces enzymatic degradation and prolongs systemic circulation via a ‘stealth’ effect that limits recognition by the mononuclear phagocyte system. Advances in polymer chemistry have yielded heterobifunctional PEGs bearing orthogonal end-groups for precise conjugation, multiarm architectures for increased drug loading and monodisperse variants to improve batch-to-batch consistency. Controlled polymerisation methods and stepwise coupling approaches now enable the production of uniform PEG chains with defined molecular weights, addressing concerns over polydispersity and potential immunogenicity. Mechanochemical and solvent-free routes have emerged to functionalise PEG under sustainable conditions, while refined analytical techniques such as mass spectrometry and chromatographic separation afford rigorous characterisation of oligomer distributions. As applications diversify to include gene delivery, immunomodulation and imaging, the interplay between PEG structure, biodistribution and therapeutic efficacy remains a central research focus. The global significance of PEG chemistry is underscored by its role in mRNA vaccines, antibody–drug conjugates and next-generation biomaterials, where bespoke polymer designs continue to drive translational innovation.

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Polyethylene Glycol Chemistry in Biomedical Applications publication trend

The graph below shows the total number of articles in polyethylene glycol chemistry in biomedical applications across all publications each year (not limited to Nature Index journals).

Technical terms

PEGylation: Covalent attachment of polyethylene glycol chains to molecules to improve solubility, stability and circulation time.

Monodisperse PEG: Polyethylene glycol with a single, uniform chain length, enhancing reproducibility and reducing immunogenic risk.

Stealth character: Property conferred by PEG coatings that reduces nanoparticle recognition and clearance by the immune system.

Pharmacokinetics: Study of the absorption, distribution, metabolism and excretion of substances within a biological system.

References

1. Versatile Route to Synthesize Heterobifunctional Poly(ethylene glycol) of Variable Functionality for Subsequent Pegylation. Polymers (2012).
2. Striving for Uniformity: A Review on Advances and Challenges To Achieve Uniform Polyethylene Glycol. Organic Process Research & Development (2024).
3. Stepwise PEG synthesis featuring deprotection and coupling in one pot. Beilstein Journal of Organic Chemistry (2021).
4. Solid-state mechanochemical ω-functionalization of poly(ethylene glycol). Beilstein Journal of Organic Chemistry (2017).
5. Separation of Molar Weight-Distributed Polyethylene Glycols by Reversed-Phase Chromatography—II. Preparative Isolation of Pure Single Homologs. Processes (2023).
6. Quantification of Polyethylene Glycol 400 Excreted in the Urine by MALDI-TOF Mass Spectrometry. Pharmaceutics (2022).