Common Polymer Found in Cosmetics Could Reduce Drug Effectiveness
Anti-PEG antibodies could hinder the effectiveness of biopharmaceuticals and may require further monitoring.
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Polyethylene glycol (PEG) is a synthetic polymer that is used in a wide variety of commercial and industrial products, including food and beverages, textiles, electronic devices, skincare and medical pharmaceuticals. The extensive use of PEG and its derivatives reflects the versatility offered by its unique properties, including the fact it is hydrophilic and biocompatible.
PEG is also used widely across the biopharmaceutical industry in drug coatings and conjugated drugs. The polymer’s characteristics can help facilitate the delivery of these complex therapeutics – which are often unstable – and reduce the clearance time from the body.
For many years, PEG was considered an entirely safe molecule with little potential for immunogenicity. This viewpoint is evolving as a growing number of animal and human studies demonstrate that people can develop anti-PEG antibodies, which are capable of recognizing PEG as a “foreign substance” and mounting an immune response. This phenomenon has been reported in individuals that are healthy and have not received PEGylated biotherapeutics.
The impact of anti-PEG antibodies on nano-carrier therapeutics and their side effects are still unclear. At the Max Planck Institute (MPI) for Polymer Research, Professor Katharina Landfester’s research group has published a new study analyzing the prevalence of these antibodies in healthy individuals and studying their impact on the cellular uptake of PEGylated nanocapsules.
"For us, PEG is interesting for coating nano-sized drug carriers," says Svenja Morsbach, a group leader in Landfester's department and a corresponding author on the paper published in Nanoscale Horizons.
Anti-PEG antibodies detected in 83% of tested population
In 2019, Morsbach and colleagues screened 500 blood samples from healthy German donors aged between 18 and 70 for anti-PEG antibodies using a technique called the enzyme-linked immunosorbent assay (ELISA). PEG antibodies were already detectable in 83% of the samples examined. The team highlighted that the older the person was, the less anti-PEG antibodies there were in their sample. “We currently assume that this is due to the increasing use of PEG in various areas of life only recently and the variation of the immune system in age," says Morsbach.
Samples of various anti-PEG antibody concentrations were then incubated with nanocapsules containing PEG, so that the research team could analyze the concentration of anti-PEG antibodies in the protein corona using liquid chromatography-mass spectrometry (LC-MS).
What is a protein corona?
The protein corona is a layer that forms around nanoparticles when they interact with proteins in a biological environment, which then determines the consequence of further protein interactions.
When the nanocapsules were tested in human and murine immune cell lines, Morsbach and colleagues found that the anti-PEG antibodies attach to the nanocapsules, effectively achieving the opposite effect of coating nanocapsules with PEG in the first place: “The nanocarrier becomes visible to the immune system and is removed before it can exert its effect," says Landfester. Ultimately, anti-PEG antibodies could reduce the effectiveness of PEG-containing drugs.
Anti-PEG antibody “supercarriers”
The researchers believe their results warrant further monitoring of anti-PEG antibody prevalence in the bloodstream. Kozma et al made a similar suggestion earlier this year in a paper exploring hypersensitivity reactions in a small number of people receiving PEG-containing mRNA COVID-19 vaccines: “Screening for anti-PEG Ab ‘supercarriers’ may help predicting reactors and thus preventing these adverse phenomena,” they suggest.
Beyond screening, Moscbrach et al say that sourcing alternatives to PEG could be a promising approach: “On the other hand, one strategy could be to find solutions that do not require PEGylation or functionalization with other polymers and create stealth behavior in other ways (e.g., protein precoating),” they write.
Reference: Deuker MFS, Mailänder V, Morsbach S, Landfester K. Anti-PEG antibodies enriched in the protein corona of PEGylated nanocarriers impact the cell uptake. Nanoscale Horiz. 2023;8(10):1377-1385. doi:10.1039/D3NH00198A
This article is a rework of a press release issued by the Max Planck Institute for Polymer Research. Material has been edited for length and content.