Journal
JOURNAL OF CONTROLLED RELEASE
Volume 224, Issue -, Pages 165-175Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.jconrel.2016.01.017
Keywords
Stroke; Fibroblast growth factor; Nanoliposome; Intranasal delivery; Blood-brain barrier
Funding
- National Natural Science Foundation of China [81360195, 81301982, 81302726, 81571392, 81272160]
- Zhejiang Provincial Foundation for Health Department [2015ZDA023]
- Medicine Grant from Wenzhou Bureau of Science and Technology [Y2014730]
- Major Scientific Project of Guangdong Province [2012A080201010]
- Science and Technology Program of Guangzhou, China [201508020001]
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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.
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