title: Intranasal delivery of bFGF with nanoliposomes enhances in vivo neuroprotection and neural injury recovery in a rodent stroke model.
abstract: 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.
authors.affiliation: Wenzhou Medical University, Wenzhou City, Zhejiang Province 325025, China; The Second Affiliated Hospital of Wenzhou Medical University, Wenzhou City, Zhejiang Province 325000, China.
authors.forename: Ying-Zheng
authors.initials: YZ
authors.lastname: Zhao
authors.affiliation: Pharmacology Research Center, Zhejiang Hisun Pharmaceutical Co., Ltd., Zhejiang Province 318000, China.
authors.forename: Min
authors.initials: M
authors.lastname: Lin
authors.affiliation: Wenzhou Medical University, Wenzhou City, Zhejiang Province 325025, China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Lin
authors.affiliation: Wenzhou Medical University, Wenzhou City, Zhejiang Province 325025, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Yang
authors.affiliation: Wenzhou Medical University, Wenzhou City, Zhejiang Province 325025, China.
authors.forename: Xi-Chong
authors.initials: XC
authors.lastname: Yu
authors.affiliation: Wenzhou Medical University, Wenzhou City, Zhejiang Province 325025, China.
authors.forename: Fu-Rong
authors.initials: FR
authors.lastname: Tian
authors.affiliation: Wenzhou Medical University, Wenzhou City, Zhejiang Province 325025, China.
authors.forename: Kai-Li
authors.initials: KL
authors.lastname: Mao
authors.affiliation: Wenzhou Medical University, Wenzhou City, Zhejiang Province 325025, China.
authors.forename: Jing-Jing
authors.initials: JJ
authors.lastname: Yang
authors.affiliation: Wenzhou Medical University, Wenzhou City, Zhejiang Province 325025, China; The Second Affiliated Hospital of Wenzhou Medical University, Wenzhou City, Zhejiang Province 325000, China. Electronic address: lctuua@sina.com.
authors.forename: Cui-Tao
authors.initials: CT
authors.lastname: Lu
authors.affiliation: Wenzhou Medical University, Wenzhou City, Zhejiang Province 325025, China; Temple University School of Pharmacy, Philadelphia, PA 19140, USA. Electronic address: ho-lun.wong@temple.edu.
authors.forename: Ho Lun
authors.initials: HL
authors.lastname: Wong
mesh_terms: D000281:Administration, Intranasal; D000818:Animals; D001812:Blood-Brain Barrier; D002544:Cerebral Infarction / Q000188:drug therapy / Q000473:pathology; D018891:Dentate Gyrus / Q000187:drug effects / Q000473:pathology; D016503:Drug Delivery Systems; D005260:Female; D016222:Fibroblast Growth Factor 2 / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000627:therapeutic use*; D008081:Liposomes; D009043:Motor Activity / Q000187:drug effects; D053758:Nanoparticles; D018696:Neuroprotective Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D020127:Recovery of Function; D015427:Reperfusion Injury / Q000188:drug therapy / Q000473:pathology; D020521:Stroke / Q000188:drug therapy* / Q000473:pathology
chemical_list: D008081:Liposomes; D018696:Neuroprotective Agents; D016222:Fibroblast Growth Factor 2
keywords: Blood–brain barrier; Fibroblast growth factor; Intranasal delivery; Nanoliposome; Stroke