Real-Time Trafficking of PEGylated Liposomes in the Rodent Focal Brain Ischemia Analyzed by Positron Emission Tomography

被引:32
作者
Fukuta, Tatsuya [1 ]
Ishii, Takayuki [1 ]
Asai, Tomohiro [1 ]
Nakamura, Genki [1 ]
Takeuchi, Yoshihito [1 ]
Sato, Akihiko [1 ]
Agato, Yurika [1 ]
Shimizu, Kosuke [1 ]
Akai, Shuji [2 ]
Fukumoto, Dai [3 ]
Harada, Norihiro [3 ]
Tsukada, Hideo [3 ]
Kawaguchi, Akira T. [4 ]
Oku, Naoto [1 ]
机构
[1] Univ Shizuoka, Dept Med Biochem, Sch Pharmaceut Sci, Shizuoka 4228526, Japan
[2] Osaka Univ, Dept Synthet Med Chem, Grad Sch Pharmaceut Sci, Osaka, Japan
[3] Hamamatsu Photon KK, Cent Res Lab, Hamamatsu, Shizuoka, Japan
[4] Tokai Univ, Sch Med, Isehara, Kanagawa 25911, Japan
基金
日本学术振兴会;
关键词
Liposome; Positron emission tomography; Ischemic stroke; Drug delivery system; Permanent middle cerebral artery occlusion; ASIALO-ERYTHROPOIETIN; STROKE; PENUMBRA; INJURY;
D O I
10.1111/aor.12350
中图分类号
R318 [生物医学工程];
学科分类号
100103 [病原生物学];
摘要
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.
引用
收藏
页码:662 / 666
页数:5
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