Six month delivery of GDNF from PLGA/vitamin E biodegradable microspheres after intravitreal injection in rabbits

Local long-term delivery of glial cell line derived neurotrophic factor (GDNF) from vitamin E/poly-lactic-co-glycolic acid microspheres (MSs) protects retinal ganglion cells in an animal model of glaucoma for up to 11 weeks. However, the pharmacokinetics of GDNF after intravitreal injection of MSs i...

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Autores: García Caballero, Cristina G., Prieto Calvo, Esther, Checa Casalengua, Patricia, García Martín, Elena Salobrar, Polo Llorens, Vicente, García Feijoo, Julián, Molina Martínez, Irene Teresa, Bravo Osuna, Irene, Herrero Vanrell, María Del Rocío
Tipo de recurso: artículo
Fecha de publicación:2017
País:España
Institución:Universidad Complutense de Madrid (UCM)
Repositorio:Docta Complutense
Idioma:inglés
OAI Identifier:oai:docta.ucm.es:20.500.14352/18740
Acceso en línea:https://hdl.handle.net/20.500.14352/18740
Access Level:acceso abierto
Palabra clave:615.4
Poly (lactic-co-glycolic acid) microspheres
Protein delivery
Vitamin E
Glial cell line-derived neurotrophic factor (GDNF)
Pharmacokinetics
Intravitreal injection.
Farmacia
Tecnología farmaceútica
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network_acronym_str ES
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repository_id_str
spelling Six month delivery of GDNF from PLGA/vitamin E biodegradable microspheres after intravitreal injection in rabbitsGarcía Caballero, Cristina G.Prieto Calvo, EstherCheca Casalengua, PatriciaGarcía Martín, Elena SalobrarPolo Llorens, VicenteGarcía Feijoo, JuliánMolina Martínez, Irene TeresaBravo Osuna, IreneHerrero Vanrell, María Del Rocío615.4Poly (lactic-co-glycolic acid) microspheresProtein deliveryVitamin EGlial cell line-derived neurotrophic factor (GDNF)PharmacokineticsIntravitreal injection.FarmaciaTecnología farmaceúticaLocal long-term delivery of glial cell line derived neurotrophic factor (GDNF) from vitamin E/poly-lactic-co-glycolic acid microspheres (MSs) protects retinal ganglion cells in an animal model of glaucoma for up to 11 weeks. However, the pharmacokinetics of GDNF after intravitreal injection of MSs is not known. We evaluated the GDNF levels after a single intravitreal injection of GDNF/VitE MSs. Biodegradable MSs were prepared by the solid-oil-in-water emulsion-solvent evaporation technique and characterized. Rabbits received a single intravitreal injection (50 μL) of GDNF/VitE MSs (4%w/v; 24 right eyes; 74.85 ng GDNF), blank MSs (4%w/v; 24 left eyes), and balanced salt solution (4 eyes). Two controls eyes received no injections. At 24 hours, 1, 4, 6, 8, 12, 18, and 24 weeks after injection, the eyes were enucleated, and the intravitreal GDNF levels were quantified. Pharmacokinetic data were analysed according to non-compartmental model. Intraocular GDNF levels of 717.1 ± 145.1 pg/mL were observed at 24 hours for GDNF-loaded MSs, followed by a plateau (745.3 ± 25.5 pg/mL) until day 28. After that, a second plateau (17.4 ± 3.7 pg/mL) occurred from 8 to 24 weeks postinjection, significantly higher than the basal levels. Eyes injected with GDNF/vitE and Blank-MSs did not show any abnormalities during the six-months follow up after administration. The single injection of GDNF/VitE MSs provided a sustained controlled release of the neurotrophic factor in a controlled fashion for up to six months.ElsevierUniversidad Complutense de Madrid20172017-05-3020172017-05-30journal articlehttp://purl.org/coar/resource_type/c_6501info:eu-repo/semantics/articleapplication/pdfhttps://hdl.handle.net/20.500.14352/18740reponame:Docta Complutenseinstname:Universidad Complutense de Madrid (UCM)Inglésengopen accesshttp://purl.org/coar/access_right/c_abf2info:eu-repo/semantics/openAccessoai:docta.ucm.es:20.500.14352/187402026-06-02T12:44:21Z
dc.title.none.fl_str_mv Six month delivery of GDNF from PLGA/vitamin E biodegradable microspheres after intravitreal injection in rabbits
title Six month delivery of GDNF from PLGA/vitamin E biodegradable microspheres after intravitreal injection in rabbits
spellingShingle Six month delivery of GDNF from PLGA/vitamin E biodegradable microspheres after intravitreal injection in rabbits
García Caballero, Cristina G.
615.4
Poly (lactic-co-glycolic acid) microspheres
Protein delivery
Vitamin E
Glial cell line-derived neurotrophic factor (GDNF)
Pharmacokinetics
Intravitreal injection.
Farmacia
Tecnología farmaceútica
title_short Six month delivery of GDNF from PLGA/vitamin E biodegradable microspheres after intravitreal injection in rabbits
title_full Six month delivery of GDNF from PLGA/vitamin E biodegradable microspheres after intravitreal injection in rabbits
title_fullStr Six month delivery of GDNF from PLGA/vitamin E biodegradable microspheres after intravitreal injection in rabbits
title_full_unstemmed Six month delivery of GDNF from PLGA/vitamin E biodegradable microspheres after intravitreal injection in rabbits
title_sort Six month delivery of GDNF from PLGA/vitamin E biodegradable microspheres after intravitreal injection in rabbits
dc.creator.none.fl_str_mv García Caballero, Cristina G.
Prieto Calvo, Esther
Checa Casalengua, Patricia
García Martín, Elena Salobrar
Polo Llorens, Vicente
García Feijoo, Julián
Molina Martínez, Irene Teresa
Bravo Osuna, Irene
Herrero Vanrell, María Del Rocío
author García Caballero, Cristina G.
author_facet García Caballero, Cristina G.
Prieto Calvo, Esther
Checa Casalengua, Patricia
García Martín, Elena Salobrar
Polo Llorens, Vicente
García Feijoo, Julián
Molina Martínez, Irene Teresa
Bravo Osuna, Irene
Herrero Vanrell, María Del Rocío
author_role author
author2 Prieto Calvo, Esther
Checa Casalengua, Patricia
García Martín, Elena Salobrar
Polo Llorens, Vicente
García Feijoo, Julián
Molina Martínez, Irene Teresa
Bravo Osuna, Irene
Herrero Vanrell, María Del Rocío
author2_role author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Universidad Complutense de Madrid
dc.subject.none.fl_str_mv 615.4
Poly (lactic-co-glycolic acid) microspheres
Protein delivery
Vitamin E
Glial cell line-derived neurotrophic factor (GDNF)
Pharmacokinetics
Intravitreal injection.
Farmacia
Tecnología farmaceútica
topic 615.4
Poly (lactic-co-glycolic acid) microspheres
Protein delivery
Vitamin E
Glial cell line-derived neurotrophic factor (GDNF)
Pharmacokinetics
Intravitreal injection.
Farmacia
Tecnología farmaceútica
description Local long-term delivery of glial cell line derived neurotrophic factor (GDNF) from vitamin E/poly-lactic-co-glycolic acid microspheres (MSs) protects retinal ganglion cells in an animal model of glaucoma for up to 11 weeks. However, the pharmacokinetics of GDNF after intravitreal injection of MSs is not known. We evaluated the GDNF levels after a single intravitreal injection of GDNF/VitE MSs. Biodegradable MSs were prepared by the solid-oil-in-water emulsion-solvent evaporation technique and characterized. Rabbits received a single intravitreal injection (50 μL) of GDNF/VitE MSs (4%w/v; 24 right eyes; 74.85 ng GDNF), blank MSs (4%w/v; 24 left eyes), and balanced salt solution (4 eyes). Two controls eyes received no injections. At 24 hours, 1, 4, 6, 8, 12, 18, and 24 weeks after injection, the eyes were enucleated, and the intravitreal GDNF levels were quantified. Pharmacokinetic data were analysed according to non-compartmental model. Intraocular GDNF levels of 717.1 ± 145.1 pg/mL were observed at 24 hours for GDNF-loaded MSs, followed by a plateau (745.3 ± 25.5 pg/mL) until day 28. After that, a second plateau (17.4 ± 3.7 pg/mL) occurred from 8 to 24 weeks postinjection, significantly higher than the basal levels. Eyes injected with GDNF/vitE and Blank-MSs did not show any abnormalities during the six-months follow up after administration. The single injection of GDNF/VitE MSs provided a sustained controlled release of the neurotrophic factor in a controlled fashion for up to six months.
publishDate 2017
dc.date.none.fl_str_mv 2017
2017-05-30
2017
2017-05-30
dc.type.none.fl_str_mv journal article
http://purl.org/coar/resource_type/c_6501
dc.type.openaire.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv https://hdl.handle.net/20.500.14352/18740
url https://hdl.handle.net/20.500.14352/18740
dc.language.none.fl_str_mv Inglés
eng
language_invalid_str_mv Inglés
language eng
dc.rights.none.fl_str_mv open access
http://purl.org/coar/access_right/c_abf2
dc.rights.openaire.fl_str_mv info:eu-repo/semantics/openAccess
rights_invalid_str_mv open access
http://purl.org/coar/access_right/c_abf2
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Elsevier
publisher.none.fl_str_mv Elsevier
dc.source.none.fl_str_mv reponame:Docta Complutense
instname:Universidad Complutense de Madrid (UCM)
instname_str Universidad Complutense de Madrid (UCM)
reponame_str Docta Complutense
collection Docta Complutense
repository.name.fl_str_mv
repository.mail.fl_str_mv
_version_ 1869412388649828352
score 15,300719

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