STERIC STABILIZATION OF MICROSPHERES WITH GRAFTED POLYETHYLENE OXIDE REDUCES PHAGOCYTOSIS BY RAT KUPFFER CELLS-INVITRO

STERIC STABILIZATION OF MICROSPHERES WITH GRAFTED POLYETHYLENE OXIDE REDUCES PHAGOCYTOSIS BY RAT KUPFFER CELLS-INVITRO
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DOI:
10.1016/0142-9612(91)90119-u
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发表时间:
1991-09-01
期刊:
影响因子:
14
通讯作者:
WATERS, JA
WATERS, JA
中科院分区:
工程技术1区
文献类型:
--
作者:
HARPER, GR;DAVIES, MC;WATERS, JA

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制备了相似尺寸(1 μ m)的空间稳定的聚环氧乙烷-聚苯乙烯共聚物微球(PS-PEO)和电荷稳定的聚苯乙烯(PS)微球,以比较通过离心淘析分离的培养的大鼠枯否细胞对它们的摄取。发现空间稳定的颗粒的吸收比电荷稳定的对照少得多。用共价接枝的PEO稳定的微球的吸收低于或等于通过非离子PEO-聚环氧丙烷(PPO-PEO)表面活性剂泊洛沙姆238或甲氧基-PEO的吸附稳定的对照微球的吸收。库普弗细胞在低温和体温(8 ℃和37 ℃)下的吞噬摄取表明PS-PEO颗粒显示出低粘附性和低代谢摄取。PEO(如泊洛沙姆238)吸附到具有共价连接或接枝PEO的颗粒上导致吸收的协同减少,其大于单独接枝和吸附的单独影响(P小于或等于0.001)。有人建议,这种组合产生了更有效的空间位阻的颗粒表面上的泊洛沙姆吸附到接枝的PEO链之间的表面。药物靶向/载体系统的相关性进行了讨论。
Sterically stabilized polyethylene oxide-polystyrene copolymer microspheres, (PS-PEO) and charge stabilized polystyrene (PS) microspheres of similar size (1-mu-m) 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.