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Exploring the relationship between anti-PEG IgM behaviors and PEGylated nanoparticles and its significance for accelerated blood clearance.
- Source :
-
Journal of controlled release : official journal of the Controlled Release Society [J Control Release] 2016 Jul 28; Vol. 234, pp. 59-67. Date of Electronic Publication: 2016 May 06. - Publication Year :
- 2016
-
Abstract
- Surface PEGylation on nanoparticles has greatly helped prolong their blood circulation half-lives. However, The injection of PEGylated nanoparticles into mice induced poly(ethylene glycol) (PEG)-specific IgM antibodies (anti-PEG IgMs), significantly changing PEG-liposomes' pharmacokinetics. In this study, we used various PEG-conjugates to conduct a mechanistic study of anti-PEG IgMs' binding behavior. The conventional belief has been that anti-PEG IgMs bind to PEG main chains; however, our findings reveal that anti-PEG IgMs did not bind to PEG main chains, whereas anti-PEG IgMs did bind to PEG-hydrophobic polymer blocks. The insertion of a hydrophilic polymer between each PEG chain and each hydrophobic polymer block suppressed anti-PEG IgMs' binding. We prove here that hydrophobic blocks are essential to anti-PEG IgMs' binding, and also that anti-PEG IgMs do not bind to intact PEGs without hydrophobic moiety. These results support our conclusion that anti-PEG IgMs exhibit specificity to PEG; however, the presence of a hydrophobic block at a proximity position from each PEG chain is essential for the binding. Also in the present study, we elucidate relations between anti-PEG IgMs and PEGylated nanoparticles. In one of our previous studies, anti-PEG IgMs scarcely affected the pharmacokinetics of PEG-b-poly(β-benzyl l-aspartate) block copolymer (PEG-PBLA) micelles, whereas anti-PEG IgMs significantly decreased PEG-liposomes' blood circulation half-life. Finally, we found that the ratio of anti-PEG IgM molecules to PEG-liposome particles is critical to these pharmacokinetic changes, and that a 10-fold increase in the number of anti-PEG IgM molecules permitted them to capture the PEG-liposome particles, thus leading to the aforementioned changes.<br /> (Copyright © 2016 Elsevier B.V. All rights reserved.)
Details
- Language :
- English
- ISSN :
- 1873-4995
- Volume :
- 234
- Database :
- MEDLINE
- Journal :
- Journal of controlled release : official journal of the Controlled Release Society
- Publication Type :
- Academic Journal
- Accession number :
- 27164541
- Full Text :
- https://doi.org/10.1016/j.jconrel.2016.05.010