Nanoparticles accumulate in ischemic core and penumbra region even when cerebral perfusion is reduced.
Nanoparticles accumulate in ischemic core and penumbra region even when cerebral perfusion is reduced.
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DOI：
10.1016/j.bbrc.2012.12.080
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发表时间：
2013-01
影响因子：
3.1
通讯作者：
Takayuki Ishii;T. Fukuta;Yurika Agato;Dai Oyama;N. Yasuda;K. Shimizu;A. Kawaguchi;T. Asai;N. Oku
中科院分区：
文献类型：
--
作者：
Takayuki Ishii;T. Fukuta;Yurika Agato;Dai Oyama;N. Yasuda;K. Shimizu;A. Kawaguchi;T. Asai;N. Oku
使用脂质体药物递送系统是一种有前途的策略，通过改变完整药物的分布来避免副作用和提高药物效率。我们以前已经表明，脂质体药物迅速积累在缺血再灌注区域和改善脑缺血再灌注损伤时，他们被注射后再灌注在短暂的大脑中动脉闭塞（t-MCAO）大鼠。在本研究中，我们假设脂质体在缺血状态下也有效地作为药物载体，因为血脑屏障的完整性在缺血事件后的早期阶段被破坏。为了验证这一假设，在永久性MCAO（p-MCAO）大鼠中观察荧光标记脂质体的脑分布。缺血后1或2 h注射脂质体，脂质体在缺血中心区和半暗带区聚集。缺血核心区的蓄积明显大于半暗带区，尽管核心区的脑血流灌注显著减少。该结果表明，即使在脑血液循环尚未恢复的情况下，使用脂质体将药物递送至缺血区域也是可能的。由于脂质体药物递送系统有可能有效地利用许多在临床试验中失败的药物，因此它们可能为中风患者提供有效的神经保护策略。
The use of a liposomal drug delivery system is a promising strategy for avoiding side effects and enhancing drug efficiency by changing the distribution of the intact drug. We have previously shown that liposomal agents quickly accumulated in an ischemia–reperfusion region and ameliorated cerebral ischemia–reperfusion injury when they were injected after reperfusion in transient middle cerebral artery occlusion (t-MCAO) rats. In the present study, we hypothesized that liposomes also act effectively as a drug carrier in the ischemic state, since the integrity of the blood brain barrier is disrupted at an early stage after an ischemic event. To test this hypothesis, the cerebral distribution of fluorescence-labeled liposomes was observed in permanent MCAO (p-MCAO) rats. The liposomes accumulated in the ischemic core and the penumbra region when injected at 1 or 2h after occlusion. The accumulation in the ischemic core region was clearly greater than that in the penumbra region, despite the cerebral blood perfusion of the core region being substantially reduced. This result suggests that drug delivery to an ischemic region using liposomes is possible even when cerebral blood circulation has not recovered. Because liposomal drug delivery systems have the potential to effectively employ a number of agents that have failed in clinical trials, they may offer an effective strategy for achieving neuroprotection in stroke patients.