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

dc.creatorScioli Montoto, Sebastián
dc.creatorSbaraglini, María Laura
dc.creatorCisneros, José Sebastián
dc.creatorChain, Cecilia Yamil
dc.creatorFerretti, Valeria Alejandra
dc.creatorLeón, Ignacio Esteban
dc.creatorAlvarez, Vera Alejandra
dc.creatorCastro, Guillermo Raúl
dc.creatorIslan, Germán Abel
dc.creatorTalevi, Alan
dc.creatorRuiz, María Esperanza
dc.date2022
dc.date2023-08-25T15:30:06Z
dc.date.accessioned2024-07-24T03:45:34Z
dc.date.available2024-07-24T03:45:34Z
dc.identifierhttp://sedici.unlp.edu.ar/handle/10915/156899
dc.identifier.urihttps://repositorioslatinoamericanos.uchile.cl/handle/2250/9535079
dc.descriptionPharmacological 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.
dc.descriptionLaboratorio de Investigación y Desarrollo de Bioactivos
dc.descriptionInstituto de Investigaciones Fisicoquímicas Teóricas y Aplicadas
dc.descriptionCentro de Química Inorgánica
dc.descriptionCentro de Investigación y Desarrollo en Fermentaciones Industriales
dc.formatapplication/pdf
dc.languageen
dc.rightshttp://creativecommons.org/licenses/by/4.0/
dc.rightsCreative Commons Attribution 4.0 International (CC BY 4.0)
dc.subjectQuímica
dc.subjectBiología
dc.subjectphenobarbital
dc.subjectdrug delivery
dc.subjectPTZ test
dc.subjectsolid lipid nanoparticles (SLNs)
dc.subjectnanostructured lipid carrier (NLC)
dc.subjectepilepsy
dc.subjectanticonvulsant
dc.subjectrelease kinetic
dc.titleNovel Phenobarbital-Loaded Nanostructured Lipid Carriers for Epilepsy Treatment: From QbD to In Vivo Evaluation
dc.typeArticulo
dc.typeArticulo


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