Nanoparticle-mediated delivery of superoxide dismutase to the brain: an effective strategy to reduce ischemia-reperfusion injury
Nanoparticle-mediated delivery of superoxide dismutase to the brain: an effective strategy to reduce ischemia-reperfusion injury
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DOI：
10.1096/fj.08-116947
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发表时间：
2009-05-01
期刊：
影响因子：
4.8
通讯作者：
Labhasetwar, Vinod
中科院分区：
文献类型：
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作者：
Reddy, Maram K.;Labhasetwar, Vinod
脑缺血和再灌注后活性氧（ROS）的过度产生通过不同的细胞和分子机制参与脑损伤，并且在缺血条件下受损的细胞抗氧化防御系统进一步加重。基于外源性递送天然形式的超氧化物歧化酶（SOD）（一种自由基清除剂）的治疗策略是有限的，因为其在体内的半衰期短（类似于6 min）和穿过血脑屏障（BBB）的渗透性差。我们将SOD包裹在可生物降解的聚（D，L-丙交酯-乙交酯）纳米颗粒（SOD-NPs）中，并在大鼠局灶性脑缺血-再灌注损伤模型中测试其疗效。我们假设，局部脑递送SOD纳米颗粒将通过中和缺血再灌注后形成的ROS的有害作用来维持SOD的保护作用。在再灌注时通过颈动脉内途径施用SOD-NP以最大化其在脑中的定位。接受SOD-NPs（10，000 U SOD/kg）的动物表现出梗死体积减少65%，而等量的SOD溶液（SOD-Sol）比盐水对照增加了25%（P
Excessive production of reactive oxygen species (ROS) after cerebral ischemia and reperfusion is implicated in brain damage through different cellular and molecular mechanisms, and it is further aggravated by impaired cellular antioxidant defense systems under ischemic conditions. Therapeutic strategies based on exogenous delivery of the native form of superoxide dismutase (SOD), a free radical scavenger, are limited because of its short half-life (similar to 6 min) in vivo and poor permeability across the blood-brain-barrier (BBB). We encapsulated SOD in biodegradable poly(D, L-lactide co-glycolide) nanoparticles (SOD-NPs) and tested their efficacy in a rat focal cerebral ischemia-reperfusion injury model. We hypothesized that localized brain delivery of SOD-NPs would sustain the protective effect of SOD by neutralizing the deleterious effects of ROS formed following ischemia-reperfusion. SOD-NPs were administered at the time of reperfusion via the intracarotid route to maximize their localization in the brain. Animals receiving SOD-NPs (10,000 U of SOD/kg) demonstrated a 65% reduction in infarct volume, whereas an equivalent dose of SOD in solution (SOD-Sol) increased it by 25% over saline control (P