Real-Time Trafficking of PEGylated Liposomes in the Rodent Focal Brain Ischemia Analyzed by Positron Emission Tomography
Real-Time Trafficking of PEGylated Liposomes in the Rodent Focal Brain Ischemia Analyzed by Positron Emission Tomography
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DOI：
10.1111/aor.12350
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发表时间：
2014-08-01
影响因子：
2.4
通讯作者：
Oku, Naoto
中科院分区：
文献类型：
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作者：
Fukuta, Tatsuya;Ishii, Takayuki;Oku, Naoto
先前，我们将脂质体给药系统应用于缺血性脑模型大鼠治疗脑缺血，我们观察到，即使永久性大脑中动脉闭塞（p-MCAO）模型大鼠的脑血流明显减少，100纳米大小的脂质体仍能在缺血性脑区域外渗和积聚。在本研究中，我们利用正电子发射断层扫描（PET）研究了1-[F-18]氟-3,6-二草四烷标记的聚乙二醇（PEG）修饰脂质体（PEG-脂质体）在p-MCAO大鼠大脑中的实时分布。闭塞1 h后，将[F-18]标记的peg -脂质体静脉注射到p-MCAO大鼠体内，2 h后进行PET扫描，PET扫描显示缺血区[F-18]的信号强度逐渐升高，但脑灌注却急剧减少，提示缺血区及其周围有peg -脂质体积累。因此，在缺血条件下，利用脂质体给药到缺血区域是可能的，脂质体给药系统可能是在缺血恢复前保护缺血脑免受损伤的一种有前途的策略。
A liposomal drug delivery system was previously applied to ischemic brain model rats for the treatment of brain ischemia, and we observed that 100-nm-sized liposomes could extravasate and accumulate in the ischemic brain region even when cerebral blood flow was markedly reduced in permanent middle cerebral artery occlusion (p-MCAO) model rats. In the present study, we investigated the real-time cerebral distribution of polyethylene glycol (PEG)-modified liposomes (PEG-liposomes) labeled with 1-[F-18]fluoro-3,6-dioxatetracosane in p-MCAO rats by positron emission tomography (PET). [F-18]-Labeled PEG-liposomes were intravenously injected into p-MCAO rats 1 h after the onset of occlusion, and then a PET scan was performed for 2 h. The PET scan showed that the signal intensity of [F-18] gradually increased in the ischemic region despite the drastic reduction in cerebral perfusion, suggesting that PEG-liposomes had accumulated in and around the ischemic region. Therefore, drug delivery to the ischemic region by use of liposomes would be possible under ischemic conditions, and a liposomal drug delivery system could be a promising strategy for protecting the ischemic brain from damage before recovery from ischemia.