title: Enhancement of nose-to-brain delivery of basic fibroblast growth factor for improving rat memory impairments induced by co-injection of β-amyloid and ibotenic acid into the bilateral hippocampus.
abstract: Basic fibroblast growth factor (bFGF) delivery to the brain of animals appears to be an emerging potential therapeutic approach to neurodegenerative diseases, such as Alzheimer's disease (AD). The intranasal route of administration could provide an alternative to intracerebroventricular infusion. A nasal spray of bFGF had been developed previously and the objective of the present study was to investigate whether bFGF nasal spray could enhance brain uptake of bFGF and ameliorate memory impairment induced by co-injection of β-amyloid(25-35) and ibotenic acid into bilateral hippocampus of rats. The results of brain uptake study showed that the AUC(0-12h) of bFGF nasal spray in olfactory bulb, cerebrum, cerebellum and hippocampus was respectively 2.47, 2.38, 2.56 and 2.19 times that of intravenous bFGF solution, and 1.11, 1.95, 1.40 and 1.93 times that of intranasal bFGF solution, indicating that intranasal administration of bFGF nasal spray was an effective means of delivering bFGF to the brain, especially to cerebrum and hippocampus. In Morris water maze tasks, intravenous administration of bFGF solution at high dose (40 μg/kg) showed little improvement on spatial memory impairment. In contrast, bFGF solution of the same dose following intranasal administration could significantly ameliorate spatial memory impairment. bFGF nasal spray obviously improved spatial memory impairment even at a dose half (20 μg/kg) of bFGF solution, recovered their acetylcholinesterase and choline acetyltransferase activity to the sham control level, and alleviated neuronal degeneration in rat hippocampus, indicating neuroprotective effects on the central nerve system. In a word, bFGF nasal spray may be a new formulation of great potential for treating AD.
authors.affiliation: Department of Pharmaceutics, School of Pharmacy, Fudan University, 826 Zhangheng Road, Shanghai 201203, People's Republic of China.
authors.forename: Chengcheng
authors.initials: C
authors.lastname: Feng
authors.forename: Chi
authors.initials: C
authors.lastname: Zhang
authors.forename: Xiayan
authors.initials: X
authors.lastname: Shao
authors.forename: Qingfeng
authors.initials: Q
authors.lastname: Liu
authors.forename: Yong
authors.initials: Y
authors.lastname: Qian
authors.forename: Liang
authors.initials: L
authors.lastname: Feng
authors.forename: Jie
authors.initials: J
authors.lastname: Chen
authors.forename: Yuan
authors.initials: Y
authors.lastname: Zha
authors.forename: Qizhi
authors.initials: Q
authors.lastname: Zhang
authors.forename: Xinguo
authors.initials: X
authors.lastname: Jiang
mesh_terms: D000110:Acetylcholinesterase / Q000378:metabolism; D000281:Administration, Intranasal; D000336:Aerosols; D016229:Amyloid beta-Peptides; D000818:Animals; D001812:Blood-Brain Barrier / Q000378:metabolism*; D002626:Chemistry, Pharmaceutical; D002795:Choline O-Acetyltransferase / Q000378:metabolism; D004195:Disease Models, Animal; D004339:Drug Compounding; D016222:Fibroblast Growth Factor 2 / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology*; D058851:GPI-Linked Proteins / Q000378:metabolism; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D006801:Humans; D007051:Ibotenic Acid; D007267:Injections; D007275:Injections, Intravenous; D008297:Male; D008568:Memory / Q000187:drug effects*; D008569:Memory Disorders / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology / Q000523:psychology; D009043:Motor Activity / Q000187:drug effects; D018696:Neuroprotective Agents / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology*; D018697:Nootropic Agents / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology*; D010446:Peptide Fragments; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins / Q000494:pharmacology; D013037:Spatial Behavior / Q000187:drug effects; D013678:Technology, Pharmaceutical / Q000379:methods
chemical_list: D000336:Aerosols; D016229:Amyloid beta-Peptides; D058851:GPI-Linked Proteins; D018696:Neuroprotective Agents; D018697:Nootropic Agents; D010446:Peptide Fragments; D011994:Recombinant Proteins; C074636:amyloid beta-protein (25-35); D016222:Fibroblast Growth Factor 2; D007051:Ibotenic Acid; D002795:Choline O-Acetyltransferase; D000110:Acetylcholinesterase; C548246:Ache protein, rat