title: Increased antiparkinson efficacy of the combined administration of VEGF- and GDNF-loaded nanospheres in a partial lesion model of Parkinson's disease.
abstract: Current research efforts are focused on the application of growth factors, such as glial cell line-derived neurotrophic factor (GDNF) and vascular endothelial growth factor (VEGF), as neuroregenerative approaches that will prevent the neurodegenerative process in Parkinson's disease. Continuing a previous work published by our research group, and with the aim to overcome different limitations related to growth factor administration, VEGF and GDNF were encapsulated in poly(lactic-co-glycolic acid) nanospheres (NS). This strategy facilitates the combined administration of the VEGF and GDNF into the brain of 6-hydroxydopamine (6-OHDA) partially lesioned rats, resulting in a continuous and simultaneous drug release. The NS particle size was about 200 nm and the simultaneous addition of VEGF NS and GDNF NS resulted in significant protection of the PC-12 cell line against 6-OHDA in vitro. Once the poly(lactic-co-glycolic acid) NS were implanted into the striatum of 6-OHDA partially lesioned rats, the amphetamine rotation behavior test was carried out over 10 weeks, in order to check for in vivo efficacy. The results showed that VEGF NS and GDNF NS significantly decreased the number of amphetamine-induced rotations at the end of the study. In addition, tyrosine hydroxylase immunohistochemical analysis in the striatum and the external substantia nigra confirmed a significant enhancement of neurons in the VEGF NS and GDNF NS treatment group. The synergistic effect of VEGF NS and GDNF NS allows for a reduction of the dose by half, and may be a valuable neurogenerative/neuroreparative approach for treating Parkinson's disease.
authors.affiliation: NanoBioCel Group, Laboratory of Pharmaceutics, University of the Basque Country (UPV/EHU), School of Pharmacy, Vitoria, Spain ; Biomedical Research Networking Center in Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Vitoria, Spain.
authors.forename: Enara
authors.initials: E
authors.lastname: Herrán
authors.affiliation: LaNCE, Department of Neurosciences, University of the Basque Country (UPV/EHU), Leioa, Spain.
authors.forename: Catalina
authors.initials: C
authors.lastname: Requejo
authors.affiliation: Department of Pharmacology, University of the Basque Country (UPV/EHU), Leioa, Spain.
authors.forename: Jose Angel
authors.initials: JA
authors.lastname: Ruiz-Ortega
authors.affiliation: Department of Pharmacology, University of the Basque Country (UPV/EHU), Leioa, Spain.
authors.forename: Asier
authors.initials: A
authors.lastname: Aristieta
authors.affiliation: NanoBioCel Group, Laboratory of Pharmaceutics, University of the Basque Country (UPV/EHU), School of Pharmacy, Vitoria, Spain ; Biomedical Research Networking Center in Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Vitoria, Spain.
authors.forename: Manoli
authors.initials: M
authors.lastname: Igartua
authors.affiliation: LaNCE, Department of Neurosciences, University of the Basque Country (UPV/EHU), Leioa, Spain.
authors.forename: Harkaitz
authors.initials: H
authors.lastname: Bengoetxea
authors.affiliation: Department of Pharmacology, University of the Basque Country (UPV/EHU), Leioa, Spain.
authors.forename: Luisa
authors.initials: L
authors.lastname: Ugedo
authors.affiliation: NanoBioCel Group, Laboratory of Pharmaceutics, University of the Basque Country (UPV/EHU), School of Pharmacy, Vitoria, Spain ; Biomedical Research Networking Center in Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Vitoria, Spain.
authors.forename: Jose Luis
authors.initials: JL
authors.lastname: Pedraz
authors.affiliation: LaNCE, Department of Neurosciences, University of the Basque Country (UPV/EHU), Leioa, Spain.
authors.forename: Jose Vicente
authors.initials: JV
authors.lastname: Lafuente
authors.affiliation: NanoBioCel Group, Laboratory of Pharmaceutics, University of the Basque Country (UPV/EHU), School of Pharmacy, Vitoria, Spain ; Biomedical Research Networking Center in Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Vitoria, Spain.
authors.forename: Rosa Maria
authors.initials: RM
authors.lastname: Hernández
mesh_terms: D000818:Animals; D000978:Antiparkinson Agents / Q000008:administration & dosage / Q000737:chemistry; D004058:Diffusion; D004338:Drug Combinations; D004357:Drug Synergism; D051100:Glial Cell Line-Derived Neurotrophic Factor / Q000008:administration & dosage* / Q000737:chemistry / Q000235:genetics; D008297:Male; D051379:Mice; D053769:Nanocapsules / Q000008:administration & dosage / Q000737:chemistry*; D054118:Nanospheres / Q000737:chemistry* / Q000648:ultrastructure; D018696:Neuroprotective Agents / Q000008:administration & dosage / Q000737:chemistry; D010300:Parkinson Disease / Q000175:diagnosis / Q000188:drug therapy* / Q000517:prevention & control*; D010316:Particle Size; D051381:Rats; D017207:Rats, Sprague-Dawley; D016896:Treatment Outcome; D042461:Vascular Endothelial Growth Factor A / Q000008:administration & dosage* / Q000737:chemistry / Q000235:genetics
chemical_list: D000978:Antiparkinson Agents; D004338:Drug Combinations; D051100:Glial Cell Line-Derived Neurotrophic Factor; D053769:Nanocapsules; D018696:Neuroprotective Agents; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A
keywords: 6-OHDA; PLGA; nanoparticles; neuroregeneration; neurotrophic factors; tyrosine hydroxylase