title: Nanotechnological strategies for nerve growth factor delivery: Therapeutic implications in Alzheimer's disease.
abstract: Alzheimer's disease (AD) is a progressive neurodegenerative disorder associated with amyloid-β peptide misfolding and aggregation. Neurotrophic factors, such as nerve growth factor (NGF), can prevent neuronal damage and rescue the cholinergic neurons that undergo cell death in AD, reverse deposition of extracellular amyloid plaques and improve cognitive deficits. However, NGF administration is hampered by the poor pharmacokinetic profile of the therapeutic protein and its inability to cross the blood-brain barrier, which requires specialised drug delivery systems (DDS) for efficient NGF delivery to the brain. This review covers the main therapeutic approaches that have been developed for NGF delivery targeting the brain, from polymeric implants to gene and cell-based therapies, focusing on the role of nanoparticulate systems for the sustained release of NGF in the brain as a neuroprotective and disease-modifying approach toward AD. Lipid- and polymer-based delivery systems, magnetic nanoparticles and quantum dots are specifically addressed as promising nanotechnological strategies to overcome the current limitations of NGF-based therapies.
authors.affiliation: Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, Universidade de Lisboa (ULisboa), Av. Prof. Gama Pinto, 1649-003 Lisbon, Portugal. Electronic address: cfaustino@ff.ulisboa.pt.
authors.forename: Célia
authors.initials: C
authors.lastname: Faustino
authors.affiliation: Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, Universidade de Lisboa (ULisboa), Av. Prof. Gama Pinto, 1649-003 Lisbon, Portugal; Universidade Lusófona's Research Center for Biosciences and Health Technologies (CBIOS), Campo Grande 376, 1749-024 Lisbon, Portugal.
authors.forename: Patrícia
authors.initials: P
authors.lastname: Rijo
authors.affiliation: Universidade Lusófona's Research Center for Biosciences and Health Technologies (CBIOS), Campo Grande 376, 1749-024 Lisbon, Portugal; Biophysics and Biomedical Engineering Institute (IBEB), Faculty of Sciences, Universidade de Lisboa, Campo Grande, 1749-016 Lisbon, Portugal.
authors.forename: Catarina Pinto
authors.initials: CP
authors.lastname: Reis
mesh_terms: D000544:Alzheimer Disease / Q000188:drug therapy* / Q000378:metabolism; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D003692:Delayed-Action Preparations / Q000737:chemistry*; D016503:Drug Delivery Systems / Q000379:methods*; D006801:Humans; D050997:Nanomedicine / Q000379:methods; D053758:Nanoparticles / Q000737:chemistry*; D036103:Nanotechnology / Q000379:methods; D020932:Nerve Growth Factor / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000627:therapeutic use
chemical_list: D003692:Delayed-Action Preparations; D020932:Nerve Growth Factor
keywords: Acetylcholine (PubChem CID: 187); Alzheimer’s disease; Amyloid-β; Drug delivery; Nanoparticles; Nerve growth factor; Neuroprotection; amyloid-beta (1-40) (PubChem CID: 71581487); amyloid-beta (1-42) (PubChem CID: 71773143)