Experimental formulation of lipid nanoparticles using polyglycerol shows reduced anti-PEG binding, indicating improved delivery efficiency.
Polyethylene glycol (PEG) is widely used to provide a stealth effect in various therapeutic applications. However, an increased occurrence of anti-PEG antibodies in patients can lead to immunological side effects and accelerated blood clearance, reducing the efficiency of PEG-based delivery vectors. One of these PEG-containing vectors is lipid nanoparticles (LNPs), which effectively deliver nucleic acids. Their high potential for treating a great number of diseases in the future was already showcased in the mRNA vaccines developed during the COVID-19 pandemic. Thus, the aim of our study was to formulate LNP systems utilizing linear polyglycerol (lPG) as an alternative stealth polymer to avoid anti-PEG antibodies while enabling mRNA delivery. Our study showed that lPG-functionalized LNPs had negligible binding to IgG anti-PEG antibodies, while successfully delivering eGFP mRNA into HepG2 cells with comparable transfection efficiency as PEGylated LNPs.
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Ensminger et al. (2025) studied this question.
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