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Antigenic Liposomes for Generation of Disease-specific Antibodies
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PEGylated liposomes: immunological responses.

Marwa Mohamed1,2, Amr S Abu Lila1,3,4, Taro Shimizu1

  • 1Department of Pharmacokinetics and Biopharmaceutics, Institute of Biomedical Sciences, Tokushima University, Tokushima, Japan.

Science and Technology of Advanced Materials
|July 6, 2019
PubMed
Summary

Polyethylene glycol (PEG)-conjugated nanocarriers can trigger immune responses, contrary to popular belief. This review examines PEG immunogenicity, accelerated blood clearance (ABC), and complement activation-related pseudoallergy (CARPA) in nanocarriers.

Keywords:
101 Self-assembly / Self-organized materials, drug delivery system30 Bio-inspired and biomedical materialsAccelerated blood clearance (ABC) phenomenonPEGylated liposomesanti-PEG IgMcomplement activationcomplement activation-related pseudoallergy (CARPA)hypersensitivity reactions (HSRs)polyethylene glycol (PEG)

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Area of Science:

  • Nanotechnology
  • Immunology
  • Toxicology

Background:

  • Polyethylene glycol (PEG) conjugation is widely believed to render nanocarriers non-immunogenic.
  • However, emerging evidence indicates that PEGylated nanocarriers can elicit significant immune responses.
  • These responses pose challenges to the safety and efficacy of nanomedicines.

Purpose of the Study:

  • To review the immunogenicity of PEGylated nanocarriers from a toxicological perspective.
  • To discuss the mechanisms and implications of the accelerated blood clearance (ABC) phenomenon.
  • To explore complement activation-related pseudoallergy (CARPA) induced by nanocarriers.

Main Methods:

  • Literature review of studies investigating immune responses to PEGylated nanocarriers.
  • Analysis of toxicological data related to PEG immunogenicity.
  • Examination of complement activation pathways and CARPA mechanisms.

Main Results:

  • PEGylated nanocarriers can induce anti-PEG antibodies, leading to accelerated blood clearance (ABC) upon repeated administration.
  • Complement activation by nanocarriers can result in CARPA, manifesting as hypersensitivity reactions.
  • Factors influencing these adverse immune interactions require careful consideration.

Conclusions:

  • The immunogenicity and CARPA reactogenicity of PEGylated nanocarriers are critical safety concerns.
  • Screening for these adverse effects is essential before clinical application of nanocarrier-based therapeutics.
  • Understanding these immune responses is crucial for the safe development of nanomedicines.