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

被引：78
作者：
Zhao, Ying-Zheng [1 ,2 ]
Lin, Min [3 ]
Lin, Qian [1 ]
Yang, Wei [1 ]
Yu, Xi-Chong [1 ]
Tian, Fu-Rong [1 ]
Mao, Kai-Li [1 ]
Yang, Jing-Jing [1 ]
Lu, Cui-Tao [1 ,2 ]
Wong, Ho Lun [1 ,4 ]
机构：
[1] Wenzhou Med Univ, Wenzhou City 325025, Zhejiang Prov, Peoples R China
[2] Wenzhou Med Univ, Affiliated Hosp 2, Wenzhou City 325000, Zhejiang Prov, Peoples R China
[3] Zhejiang Hisun Pharmaceut Co Ltd, Pharmacol Res Ctr, Taizhou 318000, Zhejiang, Peoples R China
[4] Temple Univ, Sch Pharm, 3307 N Broad St, Philadelphia, PA 19140 USA
来源：
JOURNAL OF CONTROLLED RELEASE | 2016年 / 224卷
基金：
中国国家自然科学基金;
关键词：
Stroke; Fibroblast growth factor; Nanoliposome; Intranasal delivery; Blood-brain barrier; FIBROBLAST-GROWTH-FACTOR; FOCAL CEREBRAL-ISCHEMIA; CENTRAL-NERVOUS-SYSTEM; AMERICAN-HEART-ASSOCIATION; AKT SIGNALING PATHWAYS; NASAL DRUG-DELIVERY; BLOOD-BRAIN-BARRIER; ARTERY OCCLUSION; CELLS; RATS;
D O I：
10.1016/j.jconrel.2016.01.017
中图分类号：
O6 [化学];
学科分类号：
0703 ;
摘要：
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. (C) 2016 Elsevier B.V. All rights reserved.
引用
收藏
页码：165 / 175
页数：11
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