Immunogenicity of Polyethylene Glycol (PEG)

Garay, Ricardo P.; Labaune, Jean-Pierre

doi:10.2174/2210289201102010104

Cited by 45 publications

(33 citation statements)

References 26 publications

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“…Animal studies have also reported the formation of anti-PEG antibodies on the administration of PEGylated proteins. For example, anti-PEG antibodies have been observed in the case of PEG-uricase and PEG-asparaginase resulting in a more accelerated clearance of the conjugate [163][164][165]. These are hyper-PEGylated examples with many PEG chain ends available to elicit an immune response.…”

Section: Alternatives To Pegmentioning

confidence: 99%

Pegylation and Its Impact on the Design of New Protein-Based Medicines

Ginn¹,

Khalili²,

Lever³

et al. 2014

Future Med. Chem.

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PEGylation is the covalent conjugation of PEG to therapeutic molecules. Protein PEGylation is a clinically proven approach for extending the circulation half-life and reducing the immunogenicity of protein therapeutics. Most clinically used PEGylated proteins are heterogeneous mixtures of PEG positional isomers conjugated to different residues on the protein main chain. Current research is focused to reduce product heterogeneity and to preserve bioactivity. Recent advances and possible future directions in PEGylation are described in this review. So far protein PEGylation has yielded more than 10 marketed products and in view of the lack of equally successful alternatives to extend the circulation half-life of proteins, PEGylation will still play a major role in drug delivery for many years to come.

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Section: Alternatives To Pegmentioning

confidence: 99%

Pegylation and Its Impact on the Design of New Protein-Based Medicines

Ginn¹,

Khalili²,

Lever³

et al. 2014

Future Med. Chem.

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“…PEG is often used as the hydrophilic block in block copolymers because a wide range of molecular weights are readily available and the resulting assemblies in water display PEG chains on the surface of the nanocarrier that delay the physisorption of serum proteins. Despite growing evidence of immunological responses to PEG (36, 37) that can in principle limit therapeutic efficacy, it remains a widely used hydrophilic polymer in drug formulations. Attractive alternatives include zwitterionic polymers (38) that are just emerging in polymersome applications to tumors (39).…”

Section: Nanocarrier Designmentioning

confidence: 99%

From Stealthy Polymersomes and Filomicelles to “Self” Peptide-Nanoparticles for Cancer Therapy

Oltra

Nair²,

Discher³

2014

Annu. Rev. Chem. Biomol. Eng.

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Polymersome vesicles and wormlike filomicelles self-assembled with amphiphilic, degradable block copolymers have recently shown promise in application to cancer therapy. In the case of filomicelles, dense, hydrophilic brushes of poly(ethylene glycol) on these nanoparticles combine with flexibility to nonspecifically delay clearance by phagocytes in vivo, which has motivated the development of “self” peptides that inhibit nanoparticle clearance through specific interactions. Delayed clearance, as well as robustness of polymer assemblies, opens the dosage window for delivery of increased drug loads in the polymer assemblies and increased tumor accumulation of drug(s). Antibody-targeting and combination therapies, such as with radiotherapy, are emerging in preclinical animal models of cancer. Such efforts are expected to combine with further advances in polymer composition, structure, and protein/peptide functionalization to further enhance transport through the circulation and permeation into disease sites.

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“…In addition to these hydrophobic issues, PEG also suffers oxidation damage in biological media for long-term applications [5,26,34,[44][45][46]. Furthermore, PEG antibodies occur in animals [15,34,47,48] and even humans [48], complicating clinical trials involving this material.…”

Section: Introductionmentioning

confidence: 99%