Harper G R, Davies M C, Davis S S, Tadros T F, Taylor D C, Irving M P, Waters J A
Department of Pharmaceutical Sciences, Nottingham University, UK.
Biomaterials. 1991 Sep;12(7):695-700. doi: 10.1016/0142-9612(91)90119-u.
Sterically stabilized polyethylene oxide-polystyrene copolymer microspheres, (PS-PEO) and charge stabilized polystyrene (PS) microspheres of similar size (1 micron) were prepared in order to compare their uptake by cultured rat Kupffer cells isolated by centrifugal elutriation. The uptake of the sterically stabilized particles was found to be much less than that for the charge stabilized control. The uptake of microspheres stabilized with covalently grafted PEO was lower or equivalent to that of control microspheres stabilized by the adsorption of the non-ionic PEO-polypropylene oxide (PPO-PEO) surfactant Poloxamer 238 or Methoxy-PEO. Phagocytic uptake by Kupffer cells at low and body temperature (8 degrees C and 37 degrees C) demonstrated that PS-PEO particles showed both low adherence and low metabolic uptake. The adsorption of PEO, as Poloxamer 238, to particles with covalently attached or grafted PEO resulted in a synergistic reduction in uptake that was greater than the individual effects of grafting and adsorption alone (P less than or equal to 0.001). It is suggested that this combination produces a more effective steric barrier on the particle surface with the Poloxamer adsorbing to the surface between the grafted PEO chains. The relevance to drug targeting/carrier systems is discussed.
制备了空间稳定的聚环氧乙烷 - 聚苯乙烯共聚物微球（PS - PEO）和尺寸相似（1微米）的电荷稳定聚苯乙烯（PS）微球，以便比较通过离心淘析分离的培养大鼠库普弗细胞对它们的摄取情况。发现空间稳定颗粒的摄取量远低于电荷稳定对照物的摄取量。用共价接枝PEO稳定的微球的摄取量低于或等同于通过吸附非离子型PEO - 聚环氧丙烷（PPO - PEO）表面活性剂泊洛沙姆238或甲氧基 - PEO稳定的对照微球的摄取量。在低温和体温（8℃和37℃）下库普弗细胞的吞噬摄取表明，PS - PEO颗粒表现出低粘附性和低代谢摄取。作为泊洛沙姆238的PEO吸附到具有共价连接或接枝PEO的颗粒上，导致摄取量协同降低，其大于单独接枝和吸附的个体效应（P小于或等于0.001）。有人提出，这种组合在颗粒表面产生了更有效的空间屏障，泊洛沙姆吸附在接枝的PEO链之间的表面上。讨论了其与药物靶向/载体系统的相关性。
