Zhao Jing, Chai Yu-Dong, Zhang Jing, Huang Peng-Fei, Nakashima Kenichi, Gong Yong-Kuan
Key Laboratory of Synthetic and Natural Functional Molecule Chemistry of Ministry of Education, College of Chemistry and Materials Science, Northwest University, Xi'an 710127, Shaanxi, PR China; School of Environmental and Chemical Engineering, Xi'an Polytechnic University, Xi'an 710048, Shaanxi, PR China.
Key Laboratory of Synthetic and Natural Functional Molecule Chemistry of Ministry of Education, College of Chemistry and Materials Science, Northwest University, Xi'an 710127, Shaanxi, PR China.
Acta Biomater. 2015 Apr;16:94-102. doi: 10.1016/j.actbio.2015.01.019. Epub 2015 Jan 27.
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.
由带有亲水性磷酰胆碱两性离子和细胞膜疏水十八烷基侧链的两亲性无规共聚物在水中制备了具有细胞膜模拟结构的聚合物胶束。通过动态光散射测量，聚合物胶束的流体动力学直径在80纳米至120纳米之间，ζ电位在-6.4毫伏至-2.4毫伏之间。负载6-香豆素作为荧光探针的胶束稳定性良好，可用于研究其血液循环和生物分布。使用小鼠腹腔巨噬细胞的体外吞噬结果显示，与参考胶束相比降低了10倍。新西兰兔静脉注射后，聚合物胶束的体内血液循环半衰期从0.55小时增加到90.5小时。更有趣的是，组织分布结果显示，给药48小时后，肾脏中胶束的浓度比肝脏和其他器官高4倍。这项工作的结果显示了通过使用简单的细胞膜模拟无规共聚物胶束来设计更有效的隐形药物载体的巨大前景，这种载体可以最大限度地减少网状内皮系统清除，并长时间循环以到达靶点。
