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 21days. 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.
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| http://dx.doi.org/10.1016/j.jconrel.2016.01.017 | DOI Listing |
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