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Effects of a novel pH-sensitive liposome with cleavable esterase-catalyzed and pH-responsive double smart mPEG lipid derivative on ABC phenomenon

Authors Chen D, Liu W, Shen Y, Mu H, Zhang Y, Liang R, Wang A, Sun K, Fu F

Published 20 September 2011 Volume 2011:6 Pages 2053—2061

DOI https://doi.org/10.2147/IJN.S24344

Review by Single-blind

Peer reviewer comments 3

Daquan Chen1,2, Wanhui Liu1,2, Yan Shen3, Hongjie Mu1,2, Yanchun Zhang4 , Rongcai Liang1,2, Aiping Wang1,2, Kaoxiang Sun1,2, Fenghua Fu1,2
1School of Pharmacy, Yantai University, Yantai, People’s Republic of China; 2State Key Laboratory of Long-acting and Targeting Drug Delivery System, Yantai, People’s Republic of China; 3College of Pharmacy, China Pharmaceutical University, Nanjing, People’s Republic of China; 4College of Pharmacy, Anhui University of Traditional Chinese Medicine, Hefei, People’s Republic of China

Background: The ABC phenomenon is described as a syndrome of accelerated clearance of polyethylene glycol (PEG)-modified liposomes from the bloodstream when repeatedly injected, with their increased accumulation in the liver and spleen.
Methods: To clarify this immune response phenomenon, we evaluated a novel modified pH-sensitive liposome with a cleavable double smart PEG-lipid derivative (mPEG-Hz-CHEMS).
Results: The ABC phenomenon in mice was brought about by repeated injection of conventional PEG-PE liposomes and was accompanied by a greatly increased uptake in the liver. However, a slight ABC phenomenon was brought about by repeated injection of mPEG-CHEMS liposomes and was accompanied by only a slightly increased uptake in the liver, and repeated injection of mPEG-Hz-CHEMS liposomes did not induce the ABC phenomenon and there was no increase in liver accumulation. This finding indicates that the cleavable mPEG-Hz-CHEMS derivative could lessen or eliminate the ABC phenomenon induced by repeated injection of PEGylated liposomes.
Conclusion: This research has shed some light on a solution to the ABC phenomenon using a cleavable PEG-Hz-CHEMS derivative encapsulated in nanoparticles.

Keywords: accelerated blood clearance, double smart, cleavable, mPEG-lipid derivates, pH-sensitive liposome

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