Journal
BIOMATERIALS
Volume 31, Issue 17, Pages 4757-4763Publisher
ELSEVIER SCI LTD
DOI: 10.1016/j.biomaterials.2010.02.049
Keywords
Accelerated blood clearance (ABC); Cleavable; Vesicles; Liposomes
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The accelerated blood clearance (ABC) phenomenon describes a syndrome whereby the circulation time of a second dose of injected liposomes is substantially reduced, while the hepatic and splenic accumulations increase To avoid this unexpected immune response, we have modified liposomes with cleavable PEG-lipid derivatives (PEG-CHEMS and PEG-CHMC) The ABC phenomenon was induced by repeated injection of conventional PEG-DSPE-liposomes in rat body and was accompanied by a greatly Increased uptake in the liver. In contrast, only a slight ABC phenomenon was induced by repeated injection of PEG-CHMC-liposomes and was accompanied by increased uptake in the liver Repeated injection of PEG-CHEMS-liposomes did not induce either an ABC phenomenon or an increase in liver accumulation. Repeated injection of the cleavable PEG-lipid modified vesicles (tris (hydroxymethyl) aminomethane salt of cholesteryl hemisuccinate(CHST)) showed similar results to those found with the cleavable PEG-lipid modified liposomes. These cleavable PEG-lipid derivatives could lessen or eliminate the ABC phenomenon produced by repeated injection of PEGylated liposomes or vesicles Consequently, these two cleavable PEG-lipid derivatives may not only prolong the circulation time of nanoparticles, but may also represent a solution to the ABC phenomenon (C) 2010 Elsevier Ltd All rights reserved
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