Novel Phenobarbital-Loaded Nanostructured Lipid Carriers for Epilepsy Treatment: From QbD to In Vivo Evaluation

Autores
Scioli Montoto, Sebastián; Sbaraglini, Maria Laura; Cisneros, José Sebastián; Chain, Cecilia Yamil; Ferreti, Valeria; Leon, Ignacio Esteban; Alvarez, Vera Alejandra; Castro, Guillermo Raul; Islan, German Abel; Talevi, Alan; Ruiz, María Esperanza
Año de publicación
2022
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Pharmacological treatments of central nervous system diseases are always challenging due to the restrictions imposed by the blood–brain barrier: while some drugs can effectively cross it, many others, some antiepileptic drugs among them, display permeability issues to reach the site of action and exert their pharmacological effects. The development of last-generation therapeutic nanosystems capable of enhancing drug biodistribution has gained ground in the past few years. Lipid-based nanoparticles are promising systems aimed to improve or facilitate the passage of drugs through biological barriers, which have demonstrated their effectiveness in various therapeutic fields, without signs of associated toxicity. In the present work, nanostructured lipid carriers (NLCs) containing the antiepileptic drug phenobarbital were designed and optimized by a quality by design approach (QbD). The optimized formulation was characterized by its entrapment efficiency, particle size, polydispersity index, and Z potential. Thermal properties were analyzed by DSC and TGA, and morphology and crystal properties were analyzed by AFM, TEM, and XRD. Drug localization and possible interactions between the drug and the formulation components were evaluated using FTIR. In vitro release kinetic, cytotoxicity on non-tumoral mouse fibroblasts L929, and in vivo anticonvulsant activity in an animal model of acute seizures were studied as well. The optimized formulation resulted in spherical particles with a mean size of ca. 178 nm and 98.2% of entrapment efficiency, physically stable for more than a month. Results obtained from the physicochemical and in vitro release characterization suggested that the drug was incorporated into the lipid matrix losing its crystalline structure after the synthesis process and was then released following a slower kinetic in comparison with the conventional immediate-release formulation. The NLC was non-toxic against the selected cell line and capable of delivering the drug to the site of action in an adequate amount and time for therapeutic effects, with no appreciable neurotoxicity. Therefore, the developed system represents a promising alternative for the treatment of one of the most prevalent neurological diseases, epilepsy.
Fil: Scioli Montoto, Sebastián. Universidad Nacional de La Plata. Facultad de Ciencas Exactas. Laboratorio de Investigación y Desarrollo de Bioactivos; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Investigación y Desarrollo en Fermentaciones Industriales. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Centro de Investigación y Desarrollo en Fermentaciones Industriales; Argentina
Fil: Sbaraglini, Maria Laura. Universidad Nacional de La Plata. Facultad de Ciencas Exactas. Laboratorio de Investigación y Desarrollo de Bioactivos; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata; Argentina
Fil: Cisneros, José Sebastián. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Fisicoquímicas Teóricas y Aplicadas. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Instituto de Investigaciones Fisicoquímicas Teóricas y Aplicadas; Argentina
Fil: Chain, Cecilia Yamil. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Fisicoquímicas Teóricas y Aplicadas. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Instituto de Investigaciones Fisicoquímicas Teóricas y Aplicadas; Argentina
Fil: Ferreti, Valeria. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Química Inorgánica "Dr. Pedro J. Aymonino". Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Centro de Química Inorgánica "Dr. Pedro J. Aymonino"; Argentina
Fil: Leon, Ignacio Esteban. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Química Inorgánica "Dr. Pedro J. Aymonino". Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Centro de Química Inorgánica "Dr. Pedro J. Aymonino"; Argentina
Fil: Alvarez, Vera Alejandra. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mar del Plata. Instituto de Investigaciones en Ciencia y Tecnología de Materiales. Universidad Nacional de Mar del Plata. Facultad de Ingeniería. Instituto de Investigaciones en Ciencia y Tecnología de Materiales; Argentina
Fil: Castro, Guillermo Raul. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Investigación y Desarrollo en Fermentaciones Industriales. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Centro de Investigación y Desarrollo en Fermentaciones Industriales; Argentina
Fil: Islan, German Abel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Investigación y Desarrollo en Fermentaciones Industriales. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Centro de Investigación y Desarrollo en Fermentaciones Industriales; Argentina
Fil: Talevi, Alan. Universidad Nacional de La Plata. Facultad de Ciencas Exactas. Laboratorio de Investigación y Desarrollo de Bioactivos; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata; Argentina
Fil: Ruiz, María Esperanza. Universidad Nacional de La Plata. Facultad de Ciencas Exactas. Laboratorio de Investigación y Desarrollo de Bioactivos; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata; Argentina
Materia
ANTICONVULSANT
DRUG DELIVERY
EPILEPSY
NANOSTRUCTURED LIPID CARRIER (NLC)
PHENOBARBITAL
PTZ TEST
RELEASE KINETIC
SOLID LIPID NANOPARTICLES (SLNS)
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/212005
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/212005
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Novel Phenobarbital-Loaded Nanostructured Lipid Carriers for Epilepsy Treatment: From QbD to In Vivo EvaluationScioli Montoto, SebastiánSbaraglini, Maria LauraCisneros, José SebastiánChain, Cecilia YamilFerreti, ValeriaLeon, Ignacio EstebanAlvarez, Vera AlejandraCastro, Guillermo RaulIslan, German AbelTalevi, AlanRuiz, María EsperanzaANTICONVULSANTDRUG DELIVERYEPILEPSYNANOSTRUCTURED LIPID CARRIER (NLC)PHENOBARBITALPTZ TESTRELEASE KINETICSOLID LIPID NANOPARTICLES (SLNS)https://purl.org/becyt/ford/1.4https://purl.org/becyt/ford/1Pharmacological treatments of central nervous system diseases are always challenging due to the restrictions imposed by the blood–brain barrier: while some drugs can effectively cross it, many others, some antiepileptic drugs among them, display permeability issues to reach the site of action and exert their pharmacological effects. The development of last-generation therapeutic nanosystems capable of enhancing drug biodistribution has gained ground in the past few years. Lipid-based nanoparticles are promising systems aimed to improve or facilitate the passage of drugs through biological barriers, which have demonstrated their effectiveness in various therapeutic fields, without signs of associated toxicity. In the present work, nanostructured lipid carriers (NLCs) containing the antiepileptic drug phenobarbital were designed and optimized by a quality by design approach (QbD). The optimized formulation was characterized by its entrapment efficiency, particle size, polydispersity index, and Z potential. Thermal properties were analyzed by DSC and TGA, and morphology and crystal properties were analyzed by AFM, TEM, and XRD. Drug localization and possible interactions between the drug and the formulation components were evaluated using FTIR. In vitro release kinetic, cytotoxicity on non-tumoral mouse fibroblasts L929, and in vivo anticonvulsant activity in an animal model of acute seizures were studied as well. The optimized formulation resulted in spherical particles with a mean size of ca. 178 nm and 98.2% of entrapment efficiency, physically stable for more than a month. Results obtained from the physicochemical and in vitro release characterization suggested that the drug was incorporated into the lipid matrix losing its crystalline structure after the synthesis process and was then released following a slower kinetic in comparison with the conventional immediate-release formulation. The NLC was non-toxic against the selected cell line and capable of delivering the drug to the site of action in an adequate amount and time for therapeutic effects, with no appreciable neurotoxicity. Therefore, the developed system represents a promising alternative for the treatment of one of the most prevalent neurological diseases, epilepsy.Fil: Scioli Montoto, Sebastián. Universidad Nacional de La Plata. Facultad de Ciencas Exactas. Laboratorio de Investigación y Desarrollo de Bioactivos; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Investigación y Desarrollo en Fermentaciones Industriales. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Centro de Investigación y Desarrollo en Fermentaciones Industriales; ArgentinaFil: Sbaraglini, Maria Laura. Universidad Nacional de La Plata. Facultad de Ciencas Exactas. Laboratorio de Investigación y Desarrollo de Bioactivos; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata; ArgentinaFil: Cisneros, José Sebastián. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Fisicoquímicas Teóricas y Aplicadas. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Instituto de Investigaciones Fisicoquímicas Teóricas y Aplicadas; ArgentinaFil: Chain, Cecilia Yamil. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Fisicoquímicas Teóricas y Aplicadas. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Instituto de Investigaciones Fisicoquímicas Teóricas y Aplicadas; ArgentinaFil: Ferreti, Valeria. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Química Inorgánica "Dr. Pedro J. Aymonino". Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Centro de Química Inorgánica "Dr. Pedro J. Aymonino"; ArgentinaFil: Leon, Ignacio Esteban. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Química Inorgánica "Dr. Pedro J. Aymonino". Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Centro de Química Inorgánica "Dr. Pedro J. Aymonino"; ArgentinaFil: Alvarez, Vera Alejandra. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mar del Plata. Instituto de Investigaciones en Ciencia y Tecnología de Materiales. Universidad Nacional de Mar del Plata. Facultad de Ingeniería. Instituto de Investigaciones en Ciencia y Tecnología de Materiales; ArgentinaFil: Castro, Guillermo Raul. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Investigación y Desarrollo en Fermentaciones Industriales. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Centro de Investigación y Desarrollo en Fermentaciones Industriales; ArgentinaFil: Islan, German Abel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Investigación y Desarrollo en Fermentaciones Industriales. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Centro de Investigación y Desarrollo en Fermentaciones Industriales; ArgentinaFil: Talevi, Alan. Universidad Nacional de La Plata. Facultad de Ciencas Exactas. Laboratorio de Investigación y Desarrollo de Bioactivos; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata; ArgentinaFil: Ruiz, María Esperanza. Universidad Nacional de La Plata. Facultad de Ciencas Exactas. Laboratorio de Investigación y Desarrollo de Bioactivos; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata; ArgentinaFrontiers Media2022-06info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/212005Scioli Montoto, Sebastián; Sbaraglini, Maria Laura; Cisneros, José Sebastián; Chain, Cecilia Yamil; Ferreti, Valeria; et al.; Novel Phenobarbital-Loaded Nanostructured Lipid Carriers for Epilepsy Treatment: From QbD to In Vivo Evaluation; Frontiers Media; Frontiers in Chemistry; 10; 908386; 6-2022; 1-162296-2646CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.3389/fchem.2022.908386info:eu-repo/semantics/altIdentifier/url/https://www.frontiersin.org/articles/10.3389/fchem.2022.908386/fullinfo:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T10:17:22Zoai:ri.conicet.gov.ar:11336/212005instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-09-29 10:17:22.879CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Novel Phenobarbital-Loaded Nanostructured Lipid Carriers for Epilepsy Treatment: From QbD to In Vivo Evaluation
title Novel Phenobarbital-Loaded Nanostructured Lipid Carriers for Epilepsy Treatment: From QbD to In Vivo Evaluation
spellingShingle Novel Phenobarbital-Loaded Nanostructured Lipid Carriers for Epilepsy Treatment: From QbD to In Vivo Evaluation
Scioli Montoto, Sebastián
ANTICONVULSANT
DRUG DELIVERY
EPILEPSY
NANOSTRUCTURED LIPID CARRIER (NLC)
PHENOBARBITAL
PTZ TEST
RELEASE KINETIC
SOLID LIPID NANOPARTICLES (SLNS)
title_short Novel Phenobarbital-Loaded Nanostructured Lipid Carriers for Epilepsy Treatment: From QbD to In Vivo Evaluation
title_full Novel Phenobarbital-Loaded Nanostructured Lipid Carriers for Epilepsy Treatment: From QbD to In Vivo Evaluation
title_fullStr Novel Phenobarbital-Loaded Nanostructured Lipid Carriers for Epilepsy Treatment: From QbD to In Vivo Evaluation
title_full_unstemmed Novel Phenobarbital-Loaded Nanostructured Lipid Carriers for Epilepsy Treatment: From QbD to In Vivo Evaluation
title_sort Novel Phenobarbital-Loaded Nanostructured Lipid Carriers for Epilepsy Treatment: From QbD to In Vivo Evaluation
dc.creator.none.fl_str_mv Scioli Montoto, Sebastián
Sbaraglini, Maria Laura
Cisneros, José Sebastián
Chain, Cecilia Yamil
Ferreti, Valeria
Leon, Ignacio Esteban
Alvarez, Vera Alejandra
Castro, Guillermo Raul
Islan, German Abel
Talevi, Alan
Ruiz, María Esperanza
author Scioli Montoto, Sebastián
author_facet Scioli Montoto, Sebastián
Sbaraglini, Maria Laura
Cisneros, José Sebastián
Chain, Cecilia Yamil
Ferreti, Valeria
Leon, Ignacio Esteban
Alvarez, Vera Alejandra
Castro, Guillermo Raul
Islan, German Abel
Talevi, Alan
Ruiz, María Esperanza
author_role author
author2 Sbaraglini, Maria Laura
Cisneros, José Sebastián
Chain, Cecilia Yamil
Ferreti, Valeria
Leon, Ignacio Esteban
Alvarez, Vera Alejandra
Castro, Guillermo Raul
Islan, German Abel
Talevi, Alan
Ruiz, María Esperanza
author2_role author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv ANTICONVULSANT
DRUG DELIVERY
EPILEPSY
NANOSTRUCTURED LIPID CARRIER (NLC)
PHENOBARBITAL
PTZ TEST
RELEASE KINETIC
SOLID LIPID NANOPARTICLES (SLNS)
topic ANTICONVULSANT
DRUG DELIVERY
EPILEPSY
NANOSTRUCTURED LIPID CARRIER (NLC)
PHENOBARBITAL
PTZ TEST
RELEASE KINETIC
SOLID LIPID NANOPARTICLES (SLNS)
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.4
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv Pharmacological treatments of central nervous system diseases are always challenging due to the restrictions imposed by the blood–brain barrier: while some drugs can effectively cross it, many others, some antiepileptic drugs among them, display permeability issues to reach the site of action and exert their pharmacological effects. The development of last-generation therapeutic nanosystems capable of enhancing drug biodistribution has gained ground in the past few years. Lipid-based nanoparticles are promising systems aimed to improve or facilitate the passage of drugs through biological barriers, which have demonstrated their effectiveness in various therapeutic fields, without signs of associated toxicity. In the present work, nanostructured lipid carriers (NLCs) containing the antiepileptic drug phenobarbital were designed and optimized by a quality by design approach (QbD). The optimized formulation was characterized by its entrapment efficiency, particle size, polydispersity index, and Z potential. Thermal properties were analyzed by DSC and TGA, and morphology and crystal properties were analyzed by AFM, TEM, and XRD. Drug localization and possible interactions between the drug and the formulation components were evaluated using FTIR. In vitro release kinetic, cytotoxicity on non-tumoral mouse fibroblasts L929, and in vivo anticonvulsant activity in an animal model of acute seizures were studied as well. The optimized formulation resulted in spherical particles with a mean size of ca. 178 nm and 98.2% of entrapment efficiency, physically stable for more than a month. Results obtained from the physicochemical and in vitro release characterization suggested that the drug was incorporated into the lipid matrix losing its crystalline structure after the synthesis process and was then released following a slower kinetic in comparison with the conventional immediate-release formulation. The NLC was non-toxic against the selected cell line and capable of delivering the drug to the site of action in an adequate amount and time for therapeutic effects, with no appreciable neurotoxicity. Therefore, the developed system represents a promising alternative for the treatment of one of the most prevalent neurological diseases, epilepsy.
Fil: Scioli Montoto, Sebastián. Universidad Nacional de La Plata. Facultad de Ciencas Exactas. Laboratorio de Investigación y Desarrollo de Bioactivos; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Investigación y Desarrollo en Fermentaciones Industriales. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Centro de Investigación y Desarrollo en Fermentaciones Industriales; Argentina
Fil: Sbaraglini, Maria Laura. Universidad Nacional de La Plata. Facultad de Ciencas Exactas. Laboratorio de Investigación y Desarrollo de Bioactivos; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata; Argentina
Fil: Cisneros, José Sebastián. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Fisicoquímicas Teóricas y Aplicadas. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Instituto de Investigaciones Fisicoquímicas Teóricas y Aplicadas; Argentina
Fil: Chain, Cecilia Yamil. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Fisicoquímicas Teóricas y Aplicadas. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Instituto de Investigaciones Fisicoquímicas Teóricas y Aplicadas; Argentina
Fil: Ferreti, Valeria. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Química Inorgánica "Dr. Pedro J. Aymonino". Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Centro de Química Inorgánica "Dr. Pedro J. Aymonino"; Argentina
Fil: Leon, Ignacio Esteban. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Química Inorgánica "Dr. Pedro J. Aymonino". Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Centro de Química Inorgánica "Dr. Pedro J. Aymonino"; Argentina
Fil: Alvarez, Vera Alejandra. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mar del Plata. Instituto de Investigaciones en Ciencia y Tecnología de Materiales. Universidad Nacional de Mar del Plata. Facultad de Ingeniería. Instituto de Investigaciones en Ciencia y Tecnología de Materiales; Argentina
Fil: Castro, Guillermo Raul. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Investigación y Desarrollo en Fermentaciones Industriales. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Centro de Investigación y Desarrollo en Fermentaciones Industriales; Argentina
Fil: Islan, German Abel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Investigación y Desarrollo en Fermentaciones Industriales. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Centro de Investigación y Desarrollo en Fermentaciones Industriales; Argentina
Fil: Talevi, Alan. Universidad Nacional de La Plata. Facultad de Ciencas Exactas. Laboratorio de Investigación y Desarrollo de Bioactivos; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata; Argentina
Fil: Ruiz, María Esperanza. Universidad Nacional de La Plata. Facultad de Ciencas Exactas. Laboratorio de Investigación y Desarrollo de Bioactivos; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata; Argentina
description Pharmacological treatments of central nervous system diseases are always challenging due to the restrictions imposed by the blood–brain barrier: while some drugs can effectively cross it, many others, some antiepileptic drugs among them, display permeability issues to reach the site of action and exert their pharmacological effects. The development of last-generation therapeutic nanosystems capable of enhancing drug biodistribution has gained ground in the past few years. Lipid-based nanoparticles are promising systems aimed to improve or facilitate the passage of drugs through biological barriers, which have demonstrated their effectiveness in various therapeutic fields, without signs of associated toxicity. In the present work, nanostructured lipid carriers (NLCs) containing the antiepileptic drug phenobarbital were designed and optimized by a quality by design approach (QbD). The optimized formulation was characterized by its entrapment efficiency, particle size, polydispersity index, and Z potential. Thermal properties were analyzed by DSC and TGA, and morphology and crystal properties were analyzed by AFM, TEM, and XRD. Drug localization and possible interactions between the drug and the formulation components were evaluated using FTIR. In vitro release kinetic, cytotoxicity on non-tumoral mouse fibroblasts L929, and in vivo anticonvulsant activity in an animal model of acute seizures were studied as well. The optimized formulation resulted in spherical particles with a mean size of ca. 178 nm and 98.2% of entrapment efficiency, physically stable for more than a month. Results obtained from the physicochemical and in vitro release characterization suggested that the drug was incorporated into the lipid matrix losing its crystalline structure after the synthesis process and was then released following a slower kinetic in comparison with the conventional immediate-release formulation. The NLC was non-toxic against the selected cell line and capable of delivering the drug to the site of action in an adequate amount and time for therapeutic effects, with no appreciable neurotoxicity. Therefore, the developed system represents a promising alternative for the treatment of one of the most prevalent neurological diseases, epilepsy.
publishDate 2022
dc.date.none.fl_str_mv 2022-06
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/212005
Scioli Montoto, Sebastián; Sbaraglini, Maria Laura; Cisneros, José Sebastián; Chain, Cecilia Yamil; Ferreti, Valeria; et al.; Novel Phenobarbital-Loaded Nanostructured Lipid Carriers for Epilepsy Treatment: From QbD to In Vivo Evaluation; Frontiers Media; Frontiers in Chemistry; 10; 908386; 6-2022; 1-16
2296-2646
CONICET Digital
CONICET
url http://hdl.handle.net/11336/212005
identifier_str_mv Scioli Montoto, Sebastián; Sbaraglini, Maria Laura; Cisneros, José Sebastián; Chain, Cecilia Yamil; Ferreti, Valeria; et al.; Novel Phenobarbital-Loaded Nanostructured Lipid Carriers for Epilepsy Treatment: From QbD to In Vivo Evaluation; Frontiers Media; Frontiers in Chemistry; 10; 908386; 6-2022; 1-16
2296-2646
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.3389/fchem.2022.908386
info:eu-repo/semantics/altIdentifier/url/https://www.frontiersin.org/articles/10.3389/fchem.2022.908386/full
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
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dc.publisher.none.fl_str_mv Frontiers Media
publisher.none.fl_str_mv Frontiers Media
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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score 13.070432

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