Effects of cleavable PEG-cholesterol derivatives on the accelerated blood clearance of PEGylated liposomes

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• 作者：Huan Xu ; Kai Q. Wang ; Yi H. Deng ; Da W. Chen
• 关键词：Accelerated blood clearance (ABC) ; Cleavable ; Vesicles ; Liposomes
• 刊名：Biomaterials
• 出版年：2010
• 出版时间：June 2010
• 年：2010
• 卷：31
• 期：17
• 页码：4757-4763
• 全文大小：608 K

文摘

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.