Armstrong T I, Moghimi S M, Davis S S, Illum L
Department of Pharmaceutical Sciences, University of Nottingham, UK.
Pharm Res. 1997 Nov;14(11):1629-33. doi: 10.1023/a:1012194721763.
To investigate the effect of poloxamine 908 on the MPS activity and the importance of its mode of presentation to the immune system.
Solutions of endotoxin free poloxamine 908 were injected daily intravenously to rats, and the effect on the degree of sequestration by the liver of I125 labelled, poloxamine 908-coated 60 nm polystyrene particles was investigated by studying effect of dosing regimen(s) and assessment of opsonic activity.
After 3 or 4 days repeated dosing with poloxamine 908 (0.7 mg) in solution, the poloxamine 908-coated polystyrene particles (60 nm) were rapidly cleared from the circulation. The increase sequestration of the particles by the liver lasted for more than 7 days after last dosing with the poloxamine 908 solution. In subsequent studies, it was found that a single dose of poloxamine 908 (0.7 mg) in solution was sufficient to activate the MPS 4 days after the injection. The increased uptake was found not be mediated by a serum component, nor was it due to proliferation of the Kupffer cells in the liver.
The results provide evidence that a solution of endotoxin-free poloxamine 908 activates the MPS so that 4 days after injection otherwise long-term circulating poloxamine 908-coated particles are sequestered by the liver. This finding has implications for use of such coated systems in therapeutic situations.
研究泊洛沙明908对巨噬细胞系统（MPS）活性的影响及其呈现给免疫系统的方式的重要性。
将无内毒素的泊洛沙明908溶液每日静脉注射给大鼠，通过研究给药方案的效果和评估调理活性，来研究其对肝脏对I125标记的、泊洛沙明908包被的60纳米聚苯乙烯颗粒的摄取程度的影响。
用泊洛沙明908（0.7毫克）溶液重复给药3或4天后，泊洛沙明908包被的聚苯乙烯颗粒（60纳米）迅速从循环中清除。在最后一次给予泊洛沙明908溶液后，肝脏对颗粒摄取的增加持续超过7天。在随后的研究中，发现单次注射溶液中的泊洛沙明908（0.7毫克）足以在注射后4天激活MPS。发现摄取增加不是由血清成分介导的，也不是由于肝脏中库普弗细胞的增殖。
结果提供了证据，表明无内毒素的泊洛沙明908溶液激活了MPS，使得在注射后4天，原本长期循环的泊洛沙明908包被颗粒被肝脏摄取。这一发现对这种包被系统在治疗中的应用具有启示意义。
