Intranasal delivery of bFGF with nanoliposomes enhances in vivo neuroprotection and neural injury recovery in a rodent stroke model

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• 作者：Ying-Zheng Zhao^a ; ^b ; ¹ ; Min Lin^c ; ¹ ; Qian Lin^a ; Wei Yang^a ; Xi-Chong Yu^a ; Fu-Rong Tian^a ; Kai-Li Mao^a ; Jing-Jing Yang^a ; Cui-Tao Lu^a ; ^b ; ^{lctuua@sina.com" class="auth_mail" title="E-mail the corresponding author} ; Ho Lun Wong^a ; ^d ; ^{ho-lun.wong@temple.edu" class="auth_mail" title="E-mail the corresponding author}
• 关键词：BBB ; blood&ndash ; brain barrier ; bFGF ; basic fibroblast growth factor ; bFGF-NL ; bFGF encapsulated nanoliposomes ; CCA ; common carotid artery ; CNS ; central nervous system ; ECA ; external carotid artery ; ICA ; internal carotid artery ; I/R ; ischemia&ndash ; reperfusion ; NL ; nanoliposomes ; LY ; LY294002 ; MCAO ; middle cerebral artery occlusion ; OB ; olfactory bulb
• 刊名：Journal of Controlled Release
• 出版年：2016
• 出版时间：28 February 2016
• 年：2016
• 卷：224
• 期：Complete
• 页码：165-175
• 全文大小：2459 K

文摘

Basic fibroblast growth factor (bFGF) may protect stroke patients from cerebral ischemia–reperfusion (I/R) injury. In this study, we report the intranasal use of novel nanoliposomes for the brain delivery of bFGF in a rat model of cerebral I/R. Compared with free bFGF, nanoliposomal therapy was able to significantly improve bFGF accumulation in brain tissues (p < 0.05) including the most affected ischemic penumbra regions (e.g. hippocampus, pallium). After intranasal bFGF-nanoliposomal treatment for 3 consecutive days, functional recovery as indicated by improved neurologic deficit score and spontaneous locomotor activity was observed, and the stroke infarct volume was nearly halved (p < 0.001) which persisted after 21 days. These neuroprotective effects could be blocked by the PI3-K/Akt inhibitor LY294002, indicating the involvement of PI3-K/Akt activation in the therapeutic action. Overall, our results support the intranasal use of nanoliposomal bFGF as an efficient, non-invasive means to bypass the blood–brain barrier for ischemic stroke treatment.