title: Intranasal nanoparticles of basic fibroblast growth factor for brain delivery to treat Alzheimer's disease.
abstract: Disabilities caused by neurodegeneration have become one of the main causes of mortality in elderly population, with drug distribution to the brain remaining one of the most difficult challenges in the treatment of the central nervous system (CNS) diseases due to the existence of blood-brain barrier. Lectins modified polyethylene glycol-polylactide-polyglycolide (PEG-PLGA) nanoparticles could enhance the drug delivery to the brain following intranasal administration. In this study, basic fibroblast growth factor (bFGF) was entrapped in nanoparticles conjugated with Solanum tuberosum lectin (STL), which selectively binds to N-acetylglucosamine on the nasal epithelial membrane for its brain delivery. The resulting nanoparticles had uniform particle size and negative zeta potential. The brain distribution of the formulations following intranasal administration was assessed using radioisotopic tracing method. The areas under the concentration-time curve of (125)I-bFGF in the olfactory bulb, cerebrum, and cerebellum of rats following nasal application of STL modified nanoparticles (STL-bFGF-NP) were 1.79-5.17 folds of that of rats with intravenous administration, and 0.61-2.21 and 0.19-1.07 folds higher compared with intranasal solution and unmodified nanoparticles, respectively. Neuroprotective effect was evaluated using Mirror water maze task in rats with intracerebroventricular injection of β-amyloid25-35 and ibotenic acid. The spatial learning and memory of Alzheimer's disease (AD) rats in STL-bFGF-NP group were significantly improved compared with AD model group, and were also better than other preparations. The results were consistent with the value of choline acetyltransferase activity of rat hippocampus as well as the histological observations of rat hippocampal region. The histopathology assays also confirmed the in vivo safety of STL-bFGF-NP. These results clearly indicated that STL-NP was a promising drug delivery system for peptide and protein drugs such as bFGF to enter the CNS and play the therapeutic role.
authors.affiliation: Department of Pharmaceutics, School of Pharmacy, Fudan University, Shanghai 201203, People's Republic of China; Key Laboratory of Smart Drug Delivery, Ministry of Education & PLA, 201203, People's Republic of China.
authors.forename: Chi
authors.initials: C
authors.lastname: Zhang
authors.affiliation: Department of Pharmaceutics, School of Pharmacy, Fudan University, Shanghai 201203, People's Republic of China; Key Laboratory of Smart Drug Delivery, Ministry of Education & PLA, 201203, People's Republic of China.
authors.forename: Jie
authors.initials: J
authors.lastname: Chen
authors.affiliation: Department of Pharmaceutics, School of Pharmacy, Fudan University, Shanghai 201203, People's Republic of China; Key Laboratory of Smart Drug Delivery, Ministry of Education & PLA, 201203, People's Republic of China.
authors.forename: Chengcheng
authors.initials: C
authors.lastname: Feng
authors.affiliation: Department of Pharmaceutics, School of Pharmacy, Fudan University, Shanghai 201203, People's Republic of China; Key Laboratory of Smart Drug Delivery, Ministry of Education & PLA, 201203, People's Republic of China.
authors.forename: Xiayan
authors.initials: X
authors.lastname: Shao
authors.affiliation: Department of Pharmaceutics, School of Pharmacy, Fudan University, Shanghai 201203, People's Republic of China; Key Laboratory of Smart Drug Delivery, Ministry of Education & PLA, 201203, People's Republic of China.
authors.forename: Qingfeng
authors.initials: Q
authors.lastname: Liu
authors.affiliation: Department of Pharmaceutics, School of Pharmacy, Fudan University, Shanghai 201203, People's Republic of China; Key Laboratory of Smart Drug Delivery, Ministry of Education & PLA, 201203, People's Republic of China. Electronic address: qzzhang@fudan.edu.cn.
authors.forename: Qizhi
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: Department of Pharmaceutics, School of Pharmacy, Fudan University, Shanghai 201203, People's Republic of China; Key Laboratory of Smart Drug Delivery, Ministry of Education & PLA, 201203, People's Republic of China.
authors.forename: Zhiqing
authors.initials: Z
authors.lastname: Pang
authors.affiliation: Department of Pharmaceutics, School of Pharmacy, Fudan University, Shanghai 201203, People's Republic of China; Key Laboratory of Smart Drug Delivery, Ministry of Education & PLA, 201203, People's Republic of China.
authors.forename: Xinguo
authors.initials: X
authors.lastname: Jiang
mesh_terms: D000281:Administration, Intranasal; D000544:Alzheimer Disease / Q000188:drug therapy* / Q000503:physiopathology; D000818:Animals; D019540:Area Under Curve; D001812:Blood-Brain Barrier / Q000378:metabolism; D001921:Brain / Q000378:metabolism; D004195:Disease Models, Animal; D016503:Drug Delivery Systems; D016222:Fibroblast Growth Factor 2 / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology; D006801:Humans; D007051:Ibotenic Acid / Q000008:administration & dosage / Q000494:pharmacology; D008297:Male; D053758:Nanoparticles; D018696:Neuroprotective Agents / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology; D010316:Particle Size; D037121:Plant Lectins / Q000737:chemistry; D011091:Polyesters / Q000737:chemistry; D011092:Polyethylene Glycols / Q000737:chemistry; D051381:Rats; D017207:Rats, Sprague-Dawley; D011198:Solanum tuberosum / Q000378:metabolism
chemical_list: D018696:Neuroprotective Agents; D037121:Plant Lectins; D011091:Polyesters; C000589473:polyethylene glycol-poly(lactide-co-glycolide); D016222:Fibroblast Growth Factor 2; D007051:Ibotenic Acid; D011092:Polyethylene Glycols
keywords: Alzheimer's disease (AD); Basic fibroblast growth factor (bFGF); Brain delivery; Intranasal administration; Nanoparticles; Solanum tuberosum lectin (STL)