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

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 ex...

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Autores principales: Scioli Montoto, Sebastián, Sbaraglini, María Laura, Cisneros, José Sebastián, Chain, Cecilia Yamil, Ferretti, Valeria Alejandra, León, Ignacio Esteban, Alvarez, Vera Alejandra, Castro, Guillermo Raúl, Islan, Germán Abel, Talevi, Alan, Ruiz, María Esperanza
Formato: Articulo
Lenguaje:Inglés
Publicado: 2022
Materias:
Química
Biología
phenobarbital
drug delivery
PTZ test
solid lipid nanoparticles (SLNs)
nanostructured lipid carrier (NLC)
epilepsy
anticonvulsant
release kinetic
Acceso en línea:http://sedici.unlp.edu.ar/handle/10915/156899
Aporte de:
SEDICI (UNLP) de Universidad Nacional de La Plata
id I19-R120-10915-156899
record_format dspace
spelling I19-R120-10915-1568992023-08-26T04:07:02Z http://sedici.unlp.edu.ar/handle/10915/156899 Novel Phenobarbital-Loaded Nanostructured Lipid Carriers for Epilepsy Treatment: From QbD to In Vivo Evaluation Scioli Montoto, Sebastián Sbaraglini, María Laura Cisneros, José Sebastián Chain, Cecilia Yamil Ferretti, Valeria Alejandra León, Ignacio Esteban Alvarez, Vera Alejandra Castro, Guillermo Raúl Islan, Germán Abel Talevi, Alan Ruiz, María Esperanza 2022 2023-08-25T15:30:06Z en Química Biología phenobarbital drug delivery PTZ test solid lipid nanoparticles (SLNs) nanostructured lipid carrier (NLC) epilepsy anticonvulsant release kinetic 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. Laboratorio de Investigación y Desarrollo de Bioactivos Instituto de Investigaciones Fisicoquímicas Teóricas y Aplicadas Centro de Química Inorgánica Centro de Investigación y Desarrollo en Fermentaciones Industriales Articulo Articulo http://creativecommons.org/licenses/by/4.0/ Creative Commons Attribution 4.0 International (CC BY 4.0) application/pdf
institution Universidad Nacional de La Plata
institution_str I-19
repository_str R-120
collection SEDICI (UNLP)
language Inglés
topic Química
Biología
phenobarbital
drug delivery
PTZ test
solid lipid nanoparticles (SLNs)
nanostructured lipid carrier (NLC)
epilepsy
anticonvulsant
release kinetic
spellingShingle Química
Biología
phenobarbital
drug delivery
PTZ test
solid lipid nanoparticles (SLNs)
nanostructured lipid carrier (NLC)
epilepsy
anticonvulsant
release kinetic
Scioli Montoto, Sebastián
Sbaraglini, María Laura
Cisneros, José Sebastián
Chain, Cecilia Yamil
Ferretti, Valeria Alejandra
León, Ignacio Esteban
Alvarez, Vera Alejandra
Castro, Guillermo Raúl
Islan, Germán Abel
Talevi, Alan
Ruiz, María Esperanza
Novel Phenobarbital-Loaded Nanostructured Lipid Carriers for Epilepsy Treatment: From QbD to In Vivo Evaluation
topic_facet Química
Biología
phenobarbital
drug delivery
PTZ test
solid lipid nanoparticles (SLNs)
nanostructured lipid carrier (NLC)
epilepsy
anticonvulsant
release kinetic
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.
format Articulo
Articulo
author Scioli Montoto, Sebastián
Sbaraglini, María Laura
Cisneros, José Sebastián
Chain, Cecilia Yamil
Ferretti, Valeria Alejandra
León, Ignacio Esteban
Alvarez, Vera Alejandra
Castro, Guillermo Raúl
Islan, Germán Abel
Talevi, Alan
Ruiz, María Esperanza
author_facet Scioli Montoto, Sebastián
Sbaraglini, María Laura
Cisneros, José Sebastián
Chain, Cecilia Yamil
Ferretti, Valeria Alejandra
León, Ignacio Esteban
Alvarez, Vera Alejandra
Castro, Guillermo Raúl
Islan, Germán Abel
Talevi, Alan
Ruiz, María Esperanza
author_sort Scioli Montoto, Sebastián
title Novel Phenobarbital-Loaded Nanostructured Lipid Carriers for Epilepsy Treatment: From QbD to In Vivo Evaluation
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
publishDate 2022
url http://sedici.unlp.edu.ar/handle/10915/156899
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