In vivo therapeutic gas delivery for neuroprotection with echogenic liposomes.
In vivo therapeutic gas delivery for neuroprotection with echogenic liposomes.
复制标题
使用回声脂质体进行体内治疗气体输送以实现神经保护。
DOI：
10.1161/circulationaha.109.879338
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发表时间：
2010-10-19
期刊：
影响因子：
37.8
通讯作者：
Huang, Shao-Ling
中科院分区：
文献类型：
--
作者：
Britton, George L.;Kim, Hyunggun;Kee, Patrick H.;Aronowski, Jaroslaw;Holland, Christy K.;McPherson, David D.;Huang, Shao-Ling
缺血性神经损伤是脑卒中致残的主要原因。研究表明，氙（Xe）可能是一种有效且无毒的神经保护剂。然而，由于缺乏合适的给药方法，药物递送受到阻碍。我们已经开发了一种加压冷冻的方法，封装到回声脂质体（Xe-ELIP），并调制局部气体释放与经血管超声暴露。将15微升的氩气包封到每1 mg的脂质体（70%氩气和30%氩气）中。在体外用氧-葡萄糖剥夺和对照神经元细胞评价从Xe-ELIP到细胞中的药物递送和随后的神经保护作用。在右侧大脑中动脉闭塞后，将Xe-ELIP静脉内或动脉内给予Sprague-Dawley大鼠。1-MHz的低振幅（0.18 MPa）的连续波超声引导到颈内动脉触发从循环Xe-ELIP的释放。评价了血管内注射对缺血性神经损伤和残疾的影响。将Xe-ELIP递送至氧-葡萄糖剥夺的神经元细胞在体外改善了细胞活力，并且在体内使梗死体积减少了48%。静脉内Xe-ELIP给药与颈动脉超声联合应用增强了循环Xe-ELIP的局部释放，并显示梗死体积减少了75%。这与动脉内给药后的效果相当。肢体放置、网格和横梁行走的行为测试与梗死减少相关。这种新的方法可以提供一种非侵入性的策略，超声增强局部治疗气体输送脑缺血相关的损伤，同时尽量减少全身副作用。
Ischemia-related neurologic injury is a primary cause of stroke disability. Studies have demonstrated that xenon (Xe) may have potential as an effective and nontoxic neuroprotectant. Xe delivery is, however, hampered by lack of suitable administration methods. We have developed a pressurization-freeze method to encapsulate Xe into echogenic liposomes (Xe-ELIP) and have modulated local gas release with transvascular ultrasound exposure. Fifteen microliters of Xe were encapsulated into each 1 mg of liposomes (70% Xe and 30% argon). Xe delivery from Xe-ELIP into cells and consequent neuroprotective effects were evaluated with oxygen-glucose deprived and control neuronal cells in vitro. Xe-ELIP were administered into Sprague-Dawley rats intravenously or intraarterially following right middle cerebral artery occlusion. 1-MHz low-amplitude (0.18 MPa) continuous wave ultrasound directed onto the internal carotid artery triggered Xe release from circulating Xe-ELIP. Effects of Xe delivery on ischemia-induced neurologic injury and disability were evaluated. Xe-ELIP delivery to oxygen-glucose deprived neuronal cells improved cell viability in vitro and 48% infarct volume decrease in vivo. Intravenous Xe-ELIP administration in combination with the ultrasound directed onto the carotid artery enhanced local Xe release from circulating Xe-ELIP and demonstrated 75% infarct volume reduction. This was comparable to the effect following intraarterial administration. Behavioral tests on limb placement and grid and beam walking correlated with infarct reduction. This novel methodology may provide a noninvasive strategy for ultrasound-enhanced local therapeutic gas delivery for cerebral ischemia-related injury while minimizing systemic side effects.