Polyethylene glycol, or PEG, is common in consumer products, over-the-counter medications, food, and pharmaceutical products. Concerns about PEG immunogenicity and the subsequent negative impact of pre-existing and product-induced antibodies often shadow the benefits of using PEG in nanotechnology-based products. Such anti-PEG antibodies contribute to the accelerated blood clearance of PEGylated nanomedicines and result in premature drug release and antibody-mediated toxicities. Recent data demonstrated that using PEG in COVID-19 lipid nanoparticle-mRNA vaccines is associated with an induction of anti-PEG antibodies in healthy individuals, further contributing to the development or boosting of pre-existing antibodies and increasing the risks of antibody-mediated toxicities to other products containing PEG. Therefore, monitoring the levels of pre-existing and product-induced anti-PEG antibodies provides mechanistic insights for pharmacology, toxicology, and immunological studies of PEGylated drug products.
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http://dx.doi.org/10.1007/978-1-0716-3786-9_19 | DOI Listing |
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View Article and Find Full Text PDFBiomater Sci
January 2025
Department of Bio and Brain Engineering, and KAIST Institute for Health Science and Technology, Korea Advanced Institute of Science and Technology (KAIST), Daejeon 34141, Republic of Korea.
Incorporation of polyethylene glycol (PEG) is widely used in lipid nanoparticle (LNP) formulation in order to achieve adequate stability due to its stealth properties. However, studies have detected the presence of anti-PEG neutralizing antibodies after PEGylated LNP treatment, which are associated with anaphylaxis, accelerated LNP clearance and premature release of cargo. Here, we report the development of LNPs incorporating ganglioside, a naturally occurring stealth lipid, as a PEG-free alternative.
View Article and Find Full Text PDFACS Appl Mater Interfaces
January 2025
Key Laboratory of Colloid and Interface Chemistry of the Ministry of Education, School of Chemistry and Chemical Engineering, Shandong University, Jinan, Shandong 250100, China.
We report the assembly of poly(ethylene glycol) nanoparticles (PEG NPs) and optimize their surface chemistry to minimize the formation of protein coronas and immunogenicity for improved biodistribution. PEG NPs cross-linked with disulfide bonds are synthesized utilizing zeolitic imidazolate framework-8 NPs as the templates, which are subsequently modified with PEG molecules with different end groups (carboxyl, methoxy, or amino) to vary the surface chemistry. Among the modifications, the amino and residual carboxyl groups form a pair of zwitterionic structures on the surface of PEG NPs, which minimize the adsorption of proteins (e.
View Article and Find Full Text PDFBioanalysis
January 2025
Sailstad and Associates, Inc, Durham, NC, USA.
Aims: Polyethylene glycol (PEG) is used in many applications including drug development. Due to exposure to environmental products, there is a high prevalence of preexisting anti-PEG antibodies in the global human population. The presence of anti-PEG antibodies is a concern for potentially reducing the efficacy of therapeutics after administration and represents a risk of safety events after exposure to PEGylated drug products.
View Article and Find Full Text PDFBiomater Res
December 2024
Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
The presence of anti-polyethylene glycol (anti-PEG) antibodies can hinder the therapeutic efficacy of PEGylated drugs. With the widespread use of a PEGylated coronavirus disease 2019 (COVID-19) messenger RNA vaccine (Comirnaty), the impact of pre-existing anti-PEG antibodies on vaccine potency has become a point of debate. To investigate this, we established mouse models with pre-existing anti-PEG antibodies and divided them into 3 groups: group 1 with anti-PEG immunoglobulin G + immunoglobulin M concentrations of 0.
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