Cargando…
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...
Autores principales: | , , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2022
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9428247/ https://www.ncbi.nlm.nih.gov/pubmed/36059881 http://dx.doi.org/10.3389/fchem.2022.908386 |
_version_ | 1784779071341723648 |
---|---|
author | Scioli-Montoto, Sebastian Sbaraglini, Maria Laura Cisneros, Jose Sebastian Chain, Cecilia Yamil Ferretti, Valeria León, Ignacio Esteban Alvarez, Vera Alejandra Castro, Guillermo Raul Islan, German Abel Talevi, Alan Ruiz, Maria Esperanza |
author_facet | Scioli-Montoto, Sebastian Sbaraglini, Maria Laura Cisneros, Jose Sebastian Chain, Cecilia Yamil Ferretti, Valeria León, Ignacio Esteban Alvarez, Vera Alejandra Castro, Guillermo Raul Islan, German Abel Talevi, Alan Ruiz, Maria Esperanza |
author_sort | Scioli-Montoto, Sebastian |
collection | PubMed |
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 | Online Article Text |
id | pubmed-9428247 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-94282472022-09-01 Novel Phenobarbital-Loaded Nanostructured Lipid Carriers for Epilepsy Treatment: From QbD to In Vivo Evaluation Scioli-Montoto, Sebastian Sbaraglini, Maria Laura Cisneros, Jose Sebastian Chain, Cecilia Yamil Ferretti, Valeria León, Ignacio Esteban Alvarez, Vera Alejandra Castro, Guillermo Raul Islan, German Abel Talevi, Alan Ruiz, Maria Esperanza Front Chem Chemistry 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. Frontiers Media S.A. 2022-08-17 /pmc/articles/PMC9428247/ /pubmed/36059881 http://dx.doi.org/10.3389/fchem.2022.908386 Text en Copyright © 2022 Scioli-Montoto, Sbaraglini, Cisneros, Chain, Ferretti, León, Alvarez, Castro, Islan, Talevi and Ruiz. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Chemistry Scioli-Montoto, Sebastian Sbaraglini, Maria Laura Cisneros, Jose Sebastian Chain, Cecilia Yamil Ferretti, Valeria León, Ignacio Esteban Alvarez, Vera Alejandra Castro, Guillermo Raul Islan, German Abel Talevi, Alan Ruiz, Maria Esperanza 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 |
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_short | 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 |
topic | Chemistry |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9428247/ https://www.ncbi.nlm.nih.gov/pubmed/36059881 http://dx.doi.org/10.3389/fchem.2022.908386 |
work_keys_str_mv | AT sciolimontotosebastian novelphenobarbitalloadednanostructuredlipidcarriersforepilepsytreatmentfromqbdtoinvivoevaluation AT sbaraglinimarialaura novelphenobarbitalloadednanostructuredlipidcarriersforepilepsytreatmentfromqbdtoinvivoevaluation AT cisnerosjosesebastian novelphenobarbitalloadednanostructuredlipidcarriersforepilepsytreatmentfromqbdtoinvivoevaluation AT chainceciliayamil novelphenobarbitalloadednanostructuredlipidcarriersforepilepsytreatmentfromqbdtoinvivoevaluation AT ferrettivaleria novelphenobarbitalloadednanostructuredlipidcarriersforepilepsytreatmentfromqbdtoinvivoevaluation AT leonignacioesteban novelphenobarbitalloadednanostructuredlipidcarriersforepilepsytreatmentfromqbdtoinvivoevaluation AT alvarezveraalejandra novelphenobarbitalloadednanostructuredlipidcarriersforepilepsytreatmentfromqbdtoinvivoevaluation AT castroguillermoraul novelphenobarbitalloadednanostructuredlipidcarriersforepilepsytreatmentfromqbdtoinvivoevaluation AT islangermanabel novelphenobarbitalloadednanostructuredlipidcarriersforepilepsytreatmentfromqbdtoinvivoevaluation AT talevialan novelphenobarbitalloadednanostructuredlipidcarriersforepilepsytreatmentfromqbdtoinvivoevaluation AT ruizmariaesperanza novelphenobarbitalloadednanostructuredlipidcarriersforepilepsytreatmentfromqbdtoinvivoevaluation |