PEGylated liposomes: immunological responses

• Main Authors: Marwa Mohamed, Amr S. Abu Lila, Taro Shimizu, Eman Alaaeldin, Amal Hussein, Hatem A. Sarhan, Janos Szebeni, Tatsuhiro Ishida
• Format: Article
• Language: English
• Published: Taylor & Francis Group 2019-12-01
• Series: Science and Technology of Advanced Materials
• Subjects: accelerated blood clearance (abc) phenomenon; anti-peg igm; complement activation; pegylated liposomes; polyethylene glycol (peg); complement activation-related pseudoallergy (carpa); hypersensitivity reactions (hsrs)
• Online Access: http://dx.doi.org/10.1080/14686996.2019.1627174

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.