Intranasal administration of TAT conjugated lipid nanocarriers loading GDNF for Parkinson’s disease

Parkinson’s disease (PD) is the second most common neurodegenerative disorder (ND), characterized by the loss of dopaminergic neurons, microglial activation, and neuroinflammation. Current available treatments in clinical practice cannot halt the progression of the disease. During the last few years...

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Autores: Hernando Revilla, Sara, Herrán Martínez, Enara, Figuiero-Silva, Joana, Pedraz Muñoz, José Luis, Igartua Olaechea, Manuela, Carro, Eva, Hernández Martín, Rosa María
Tipo de recurso: artículo
Fecha de publicación:2017
País:España
Institución:Universidad del País Vasco
Repositorio:Addi. Archivo Digital para la Docencia y la Investigación
OAI Identifier:oai:addi.ehu.eus:10810/74903
Acceso en línea:http://hdl.handle.net/10810/74903
Access Level:acceso abierto
Palabra clave:Parkinson's disease
glial derived neurotrophic factor (GDNF)
TAT peptide
neuroprotection
nanostructured lipid carriers (NLC)
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spelling Intranasal administration of TAT conjugated lipid nanocarriers loading GDNF for Parkinson’s diseaseHernando Revilla, SaraHerrán Martínez, EnaraFiguiero-Silva, JoanaPedraz Muñoz, José LuisIgartua Olaechea, ManuelaCarro, EvaHernández Martín, Rosa MaríaParkinson's diseaseglial derived neurotrophic factor (GDNF)TAT peptideneuroprotectionnanostructured lipid carriers (NLC)Parkinson’s disease (PD) is the second most common neurodegenerative disorder (ND), characterized by the loss of dopaminergic neurons, microglial activation, and neuroinflammation. Current available treatments in clinical practice cannot halt the progression of the disease. During the last few years, growth factors (GFs) have been raised as a promising therapeutic approach to address the underlying neurodegenerative process. Among others, glial cell-derived neurotrophic factor (GDNF) is a widely studied GF for PD. However, its clinical use is limited due to its short half life, rapid degradation rate, and difficulties in crossing the blood-brain barrier (BBB). Lately, intranasal administration has appeared as an alternative non-invasive way to bypass the BBB and target drugs directly to the central nervous system (CNS). Thus, the aim of this work was to develop a novel nanoformulation to enhance brain targeting in PD through nasal administration. For that purpose, GDNF was encapsulated into chitosan (CS)-coated nanostructured lipid carriers, with the surface modified with transactivator of transcription (TAT) peptide (CS-nanostructured lipid carrier (NLC)-TAT-GDNF). After the physiochemical characterization of nanoparticles, the in vivo study was performed by intranasal administration to a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model of PD. The CS-NLC-TAT-GDNF-treated group revealed motor recovery which was confirmed with immunohistochemistry studies, showing the highest number of tyrosine hydroxylase (TH+) fibers in the striatum and TH+ neuron levels in the substantia nigra. Moreover, ionizing calcium-binding adaptor molecule 1 immunohistochemistry was performed, revealing that CS-NLC-TAT-GDNF acts as a modulator on microglia activation, obtaining values similar to control. Therefore, it may be concluded that the intranasal administration of CS-NLC-TAT-GDNF may represent a promising therapy for PD treatment.This project was partially supported by the “Ministerio de Economía y Competitividad” (SAF2013-42347-R), the University of the Basque Country (UPV/EHU) (UFI 11/32), and the FEDER funds. The authors thank SGIker of UPV/EHU and European funding (ERDF and ESF) for technical and human support. The authors also wish to thank the intellectual and technical assistance from the ICTS “NANBIOSIS”, more specifically by the Drug Formulation Unit (U10) of the CIBER-BBN at the UPV/EHU.Springer202520252017info:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10810/74903reponame:Addi. Archivo Digital para la Docencia y la Investigacióninstname:Universidad del País VascoInglésinfo:eu-repo/grantAgreement/MINECO/SAF2013-42347-R/https://doi.org/10.1007/s12035-017-0728-7info:eu-repo/semantics/openAccess© 2017, Springer Science Business Media, LLCoai:addi.ehu.eus:10810/749032026-06-18T09:23:17Z
dc.title.none.fl_str_mv Intranasal administration of TAT conjugated lipid nanocarriers loading GDNF for Parkinson’s disease
title Intranasal administration of TAT conjugated lipid nanocarriers loading GDNF for Parkinson’s disease
spellingShingle Intranasal administration of TAT conjugated lipid nanocarriers loading GDNF for Parkinson’s disease
Hernando Revilla, Sara
Parkinson's disease
glial derived neurotrophic factor (GDNF)
TAT peptide
neuroprotection
nanostructured lipid carriers (NLC)
title_short Intranasal administration of TAT conjugated lipid nanocarriers loading GDNF for Parkinson’s disease
title_full Intranasal administration of TAT conjugated lipid nanocarriers loading GDNF for Parkinson’s disease
title_fullStr Intranasal administration of TAT conjugated lipid nanocarriers loading GDNF for Parkinson’s disease
title_full_unstemmed Intranasal administration of TAT conjugated lipid nanocarriers loading GDNF for Parkinson’s disease
title_sort Intranasal administration of TAT conjugated lipid nanocarriers loading GDNF for Parkinson’s disease
dc.creator.none.fl_str_mv Hernando Revilla, Sara
Herrán Martínez, Enara
Figuiero-Silva, Joana
Pedraz Muñoz, José Luis
Igartua Olaechea, Manuela
Carro, Eva
Hernández Martín, Rosa María
author Hernando Revilla, Sara
author_facet Hernando Revilla, Sara
Herrán Martínez, Enara
Figuiero-Silva, Joana
Pedraz Muñoz, José Luis
Igartua Olaechea, Manuela
Carro, Eva
Hernández Martín, Rosa María
author_role author
author2 Herrán Martínez, Enara
Figuiero-Silva, Joana
Pedraz Muñoz, José Luis
Igartua Olaechea, Manuela
Carro, Eva
Hernández Martín, Rosa María
author2_role author
author
author
author
author
author
dc.subject.none.fl_str_mv Parkinson's disease
glial derived neurotrophic factor (GDNF)
TAT peptide
neuroprotection
nanostructured lipid carriers (NLC)
topic Parkinson's disease
glial derived neurotrophic factor (GDNF)
TAT peptide
neuroprotection
nanostructured lipid carriers (NLC)
description Parkinson’s disease (PD) is the second most common neurodegenerative disorder (ND), characterized by the loss of dopaminergic neurons, microglial activation, and neuroinflammation. Current available treatments in clinical practice cannot halt the progression of the disease. During the last few years, growth factors (GFs) have been raised as a promising therapeutic approach to address the underlying neurodegenerative process. Among others, glial cell-derived neurotrophic factor (GDNF) is a widely studied GF for PD. However, its clinical use is limited due to its short half life, rapid degradation rate, and difficulties in crossing the blood-brain barrier (BBB). Lately, intranasal administration has appeared as an alternative non-invasive way to bypass the BBB and target drugs directly to the central nervous system (CNS). Thus, the aim of this work was to develop a novel nanoformulation to enhance brain targeting in PD through nasal administration. For that purpose, GDNF was encapsulated into chitosan (CS)-coated nanostructured lipid carriers, with the surface modified with transactivator of transcription (TAT) peptide (CS-nanostructured lipid carrier (NLC)-TAT-GDNF). After the physiochemical characterization of nanoparticles, the in vivo study was performed by intranasal administration to a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model of PD. The CS-NLC-TAT-GDNF-treated group revealed motor recovery which was confirmed with immunohistochemistry studies, showing the highest number of tyrosine hydroxylase (TH+) fibers in the striatum and TH+ neuron levels in the substantia nigra. Moreover, ionizing calcium-binding adaptor molecule 1 immunohistochemistry was performed, revealing that CS-NLC-TAT-GDNF acts as a modulator on microglia activation, obtaining values similar to control. Therefore, it may be concluded that the intranasal administration of CS-NLC-TAT-GDNF may represent a promising therapy for PD treatment.
publishDate 2017
dc.date.none.fl_str_mv 2017
2025
2025
dc.type.none.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv http://hdl.handle.net/10810/74903
url http://hdl.handle.net/10810/74903
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv info:eu-repo/grantAgreement/MINECO/SAF2013-42347-R/
https://doi.org/10.1007/s12035-017-0728-7
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
© 2017, Springer Science Business Media, LLC
eu_rights_str_mv openAccess
rights_invalid_str_mv © 2017, Springer Science Business Media, LLC
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Springer
publisher.none.fl_str_mv Springer
dc.source.none.fl_str_mv reponame:Addi. Archivo Digital para la Docencia y la Investigación
instname:Universidad del País Vasco
instname_str Universidad del País Vasco
reponame_str Addi. Archivo Digital para la Docencia y la Investigación
collection Addi. Archivo Digital para la Docencia y la Investigación
repository.name.fl_str_mv
repository.mail.fl_str_mv
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