Mohamed, Marwa Tokushima University|Minia University
Lila, Amr S. Abu Tokushima University|Zagazig University|Hail University
Alaaeldin, Eman Minia University
Hussein, Amal Minia University
Sarhan, Hatem A. Minia University
Szebeni, Janos Semmelweis University|SeroScience LCC.
Accelerated blood clearance (ABC) phenomenon
polyethylene glycol (PEG)
complement activation-related pseudoallergy (CARPA)
hypersensitivity reactions (HSRs)
A commonly held view is that nanocarriers conjugated to polyethylene glycol (PEG) are non-immunogenic. However, many studies have reported that unexpected immune responses have occurred against PEG-conjugated nanocarriers. One unanticipated response is the rapid clearance of PEGylated nanocarriers upon repeat administration, called the accelerated blood clearance (ABC) phenomenon. ABC involves the production of antibodies toward nanocarrier components, including PEG, which reduces the safety and effectiveness of encapsulated therapeutic agents. Another immune response is the hypersensitivity or infusion reaction referred to as complement (C) activation-related pseudoallergy (CARPA). Such immunogenicity and adverse reactivities of PEGylated nanocarriers may be of potential concern for the clinical use of PEGylated therapeutics. Accordingly, screening of the immunogenicity and CARPA reactogenicity of nanocarrier-based therapeutics should be a prerequisite before they can proceed into clinical studies. This review presents PEGylated liposomes, immunogenicity of PEG, the ABC phenomenon, C activation and lipid-induced CARPA from a toxicological point of view, and also addresses the factors that influence these adverse interactions with the immune system.
Science and Technology of Advanced Materials
Taylor & Francis|National Institute for Materials Science
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
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