In vitro cell interaction and in vivo biodistribution of poly(lactide-co-glycolide) nanospheres surface modified by poloxamer and poloxamine copolymers
In vitro cell interaction and in vivo biodistribution of poly(lactide-co-glycolide) nanospheres surface modified by poloxamer and poloxamine copolymers
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DOI：
10.1016/s0168-3659(96)01504-0
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发表时间：
1997-02-01
影响因子：
10.8
通讯作者：
Illum, L
中科院分区：
文献类型：
--
作者：
Dunn, SE;Coombes, AGA;Illum, L
使用界面聚合物沉积（纳米沉淀）方法，已经生产了尺寸范围为80-150 nm的可生物降解的聚（丙交酯-共-乙交酯）（PLGA）纳米球。通过吸附泊洛沙姆和泊洛沙胺系列（泊洛沙姆407、泊洛沙胺904和泊洛沙胺908）的聚环氧丙烷-聚环氧乙烷（PPO-PEO）嵌段共聚物或通过在生产过程中将相同的共聚物掺入纳米球中，用聚乙二醇（PEG）对纳米球进行表面改性。在纳米球生产过程中，通过掺入铟-111 - 8-羟基喹啉对纳米球进行放射性标记。PLGA纳米球系统的生物学行为进行了讨论，在体外细胞与分离的非实质肝细胞的相互作用和在体内的生物分布在大鼠和兔模型静脉注射后。将结果与以相同方式表面改性的模型聚苯乙烯纳米球的结果进行比较。显示了用泊洛沙姆407或泊洛沙胺908涂覆的PLGA纳米球在静脉内注射给大鼠后表现出延长的血液循环时间，伴随着肝脏和脾脏累积的组合减少。静脉注射后3小时，39%和28%的泊洛沙姆407和泊洛沙胺908包衣的PLGA纳米球的给药剂量保留在血液循环中。
Biodegradable poly(lactide-co-glycolide) (PLGA) nanospheres in the size range 80-150 nm have been produced, using an interfacial polymer deposition (nanoprecipitation) method. The nanospheres have been surface modified with poly(ethylene glycol) (PEG) either by adsorption of polypropylene oxide-polyethylene oxide (PPO-PEO) block copolymers of the poloxamer and poloxamine series (poloxamer 407, poloxamine 904 and poloxamine 908) or by incorporation of the same copolymers into the nanospheres during the production. The nanospheres were radiolabelled by incorporation of indium-111-oxine during nanosphere production. The biological behaviour of the PLGA nanosphere systems is discussed in terms of the in vitro cell interaction with isolated non-parenchymal liver cells and the in vivo biodistribution in the rat and rabbit models after intravenous injection. The results are compared to those for model polystyrene nanospheres surface modified in the same manner. It is shown that PLGA nanospheres coated with poloxamer 407 or poloxamine 908 exhibit prolonged blood circulation times accompanied by a combined reduction in liver and spleen accumulation after intravenous injection to the rat. Three hours post intravenous injection, 39% and 28% of the administered dose of poloxamer 407- and poloxamine 908-coated PLGA nanospheres remains in the blood circulation.