Acta Biomaterialia 2015-04-01

Long circulating micelles of an amphiphilic random copolymer bearing cell outer membrane phosphorylcholine zwitterions.

Jing Zhao, Yu-Dong Chai, Jing Zhang, Peng-Fei Huang, Kenichi Nakashima, Yong-Kuan Gong

文献索引：Acta Biomater. 16 , 94-102, (2015)

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摘要

Polymeric micelles with cell outer membrane mimetic structure were prepared in water from amphiphilic random copolymers bearing both the hydrophilic phosphorylcholine zwitterions and hydrophobic octadecyl side chains of cell outer membrane. The polymeric micelles showed sizes ranging from 80 nm to 120 nm in hydrodynamic diameter and zeta-potentials from -6.4 mV to -2.4 mV by dynamic light scattering measurements. The micelles loaded with 6-coumarin as a fluorescence probe were stable to investigate their blood circulation and biodistribution. The in vitro phagocytosis results using murine peritoneal macrophages showed 10-fold reduction compared with a reference micelle. The in vivo blood circulation half-life of the polymeric micelles following intravenous administration in New Zealand Rabbits was increased from 0.55 h to 90.5h. More interestingly, tissue distribution results showed that the concentration of the micelles in the kidney is 4-fold higher than that in the liver and other organs 48 h after administration. The results of this work show great promise for designing more effective stealth drug carriers that can minimize reticuloendothelial system clearance and circulate for long time to reach target by using simple cell membrane mimetic random copolymer micelles.Copyright © 2015 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.