Relationship between the concentration of anti-polyethylene glycol (PEG) immunoglobulin M (IgM) and the intensity of the accelerated blood clearance (ABC) phenomenon against PEGylated liposomes in mice

Biological & Pharmaceutical Bulletin
Yosuke HashimotoHiroshi Kiwada

Abstract

PEGylation, which is the surface modification of nanocarriers with polyethylene glycol (PEG), has increased the circulation time and reduced the immunogenic responses to nanocarriers. However, many reports have demonstrated that the intravenous injection of sterically stabilized PEGylated liposome (SL) causes an accelerated blood clearance (ABC) of subsequent doses via anti-PEG immunoglobulin M (IgM)-mediated complement activation. In the present study, the relationships between serum anti-PEG IgM concentration, the intensity of complement activation and the hepatic clearance of SL were quantitatively investigated for their role in the ABC phenomenon. Interestingly, with increasing serum anti-PEG IgM concentrations, the intensity of complement activation increased linearly, while the intensity of the hepatic clearance of SL was increased and then saturated. In addition, only 15-17% of anti-PEG IgM in blood circulation induced by SL at different doses was associated with a second dose SL. The present results indicate that it is the hepatic uptake of SL that is the limiting step in the ABC phenomenon, rather than the association of anti-PEG IgM to the SL and a subsequent complement activation.

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Citations

Jan 3, 2016·Cellular Immunology·Mathieu IngUNKNOWN ABIRISK consortium
Feb 3, 2016·Biological & Pharmaceutical Bulletin·Masami UkawaTatsuhiro Ishida
Jan 17, 2016·Toxicology and Applied Pharmacology·Anna N Ilinskaya, Marina A Dobrovolskaia
Jul 18, 2015·Journal of Controlled Release : Official Journal of the Controlled Release Society·Vítor M GasparIlídio J Correia
Sep 16, 2015·Wiley Interdisciplinary Reviews. Nanomedicine and Nanobiotechnology·Yingwei WuXiaofeng Tao
Nov 1, 2018·Drug Delivery and Translational Research·Yuqing SuYihui Deng
Jul 17, 2020·Wiley Interdisciplinary Reviews. Nanomedicine and Nanobiotechnology·Marina A Dobrovolskaia, Mark Bathe
Jul 6, 2019·Science and Technology of Advanced Materials·Marwa MohamedTatsuhiro Ishida
Oct 24, 2018·Nature Nanotechnology·Janos SzebeniMarina A Dobrovolskaia
Nov 6, 2018·Journal of Pharmaceutical Sciences·Dongfen YuanYanguang Cao
Feb 28, 2021·European Journal of Pharmaceutics and Biopharmaceutics : Official Journal of Arbeitsgemeinschaft Für Pharmazeutische Verfahrenstechnik E.V·Soma PatnaikPrashant Kesharwani
May 8, 2020·European Journal of Pharmaceutics and Biopharmaceutics : Official Journal of Arbeitsgemeinschaft Für Pharmazeutische Verfahrenstechnik E.V·Nehal E ElsadekTatsuhiro Ishida
Jul 12, 2019·Advanced Drug Delivery Reviews·Raziye MohammadpourHamidreza Ghandehari
Apr 24, 2021·Drug Discovery Today·Vincent LebretonFrederic Lagarce
May 9, 2016·ACS Biomaterials Science & Engineering·Sourabh ShuklaNicole F Steinmetz

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