Lipid Nanoparticles with Stiripentol and Cannabidiol Oil: From Rational Optimization to Preclinical Characterization

Autores
Scioli Montoto, Sebastián; Lobos, Martín; Melis, Mauricio Ezequiel; Ruatta, Santiago; Muraca, Giuliana; Chain, Cecilia Yamil; Cisneros, José Sebastián; Álvarez, Vera Alejandra; Islan, Germán Abel; Talevi, Alan; Ruiz, María Esperanza
Año de publicación
2026
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Background/Objectives: Dravet Syndrome (DS) is a severe form of epilepsy that typically manifests in the first year of life and often requires polytherapy with two or more anti- seizure medications (ASMs) to achieve adequate seizure control. Whereas the combination of stiripentol (STP) and cannabidiol (CBD) has demonstrated clinical efficacy, it presents significant formulation challenges due to the low aqueous solubility and poor oral bioavail- ability of both compounds. Furthermore, the high daily dosages of STP (approximately 50 mg/kg/day or higher) and the oily nature of conventional CBD formulations often hinder patient compliance, as pediatric patients frequently reject these treatments due to unfavorable organoleptic properties. Methods: Nanostructured lipid carriers (NLCs) con- taining STP and CBD suspended in an aqueous medium were developed. The formulation was optimized using Response Surface Methodology (RSM) and subjected to comprehen- sive in vitro and in vivo characterization. Results: The optimized formulation exhibited a mean particle size of 175.3 nm, a polydispersity index (PDI) of 0.232, a zeta potential of −8.35 mV, and an encapsulation efficiency greater than 99% for both drugs. Physico- chemical characterization via atomic force microscopy, differential scanning calorimetry, thermogravimetric analysis, X-ray diffraction, and Fourier transform infrared spectroscopy revealed spherical nanoparticles without aggregation, with the drugs molecularly dis- persed within the lipid matrix. Both STP and CBD showed sustained release profiles and demonstrated oral pharmacokinetic profiles that were comparable or superior to current commercial products. Conclusions: This novel formulation represents a promising thera- peutic alternative for DS, enabling the co-administration of STP and CBD while potentially enhancing CBD bioavailability and treatment adherence in pediatric populations.
Laboratorio de Investigación y Desarrollo de Bioactivos
Materia
Bioquímica
Cannabidiol
Dravet syndrome
Lipid nanoparticles
Nanostructured lipid carriers
Oral administration
Pediatric formulations
Pharmacokinetic study
Release profile
Response surface
Stiripentol
Nivel de accesibilidad
acceso abierto
Condiciones de uso
http://creativecommons.org/licenses/by/4.0/
Repositorio
SEDICI (UNLP)
Institución
Universidad Nacional de La Plata
OAI Identificador
oai:sedici.unlp.edu.ar:10915/195987
Acceder
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oai_identifier_str oai:sedici.unlp.edu.ar:10915/195987
network_acronym_str SEDICI
repository_id_str 1329
network_name_str SEDICI (UNLP)
spelling Lipid Nanoparticles with Stiripentol and Cannabidiol Oil: From Rational Optimization to Preclinical CharacterizationScioli Montoto, SebastiánLobos, MartínMelis, Mauricio EzequielRuatta, SantiagoMuraca, GiulianaChain, Cecilia YamilCisneros, José SebastiánÁlvarez, Vera AlejandraIslan, Germán AbelTalevi, AlanRuiz, María EsperanzaBioquímicaCannabidiolDravet syndromeLipid nanoparticlesNanostructured lipid carriersOral administrationPediatric formulationsPharmacokinetic studyRelease profileResponse surfaceStiripentolBackground/Objectives: Dravet Syndrome (DS) is a severe form of epilepsy that typically manifests in the first year of life and often requires polytherapy with two or more anti- seizure medications (ASMs) to achieve adequate seizure control. Whereas the combination of stiripentol (STP) and cannabidiol (CBD) has demonstrated clinical efficacy, it presents significant formulation challenges due to the low aqueous solubility and poor oral bioavail- ability of both compounds. Furthermore, the high daily dosages of STP (approximately 50 mg/kg/day or higher) and the oily nature of conventional CBD formulations often hinder patient compliance, as pediatric patients frequently reject these treatments due to unfavorable organoleptic properties. Methods: Nanostructured lipid carriers (NLCs) con- taining STP and CBD suspended in an aqueous medium were developed. The formulation was optimized using Response Surface Methodology (RSM) and subjected to comprehen- sive in vitro and in vivo characterization. Results: The optimized formulation exhibited a mean particle size of 175.3 nm, a polydispersity index (PDI) of 0.232, a zeta potential of −8.35 mV, and an encapsulation efficiency greater than 99% for both drugs. Physico- chemical characterization via atomic force microscopy, differential scanning calorimetry, thermogravimetric analysis, X-ray diffraction, and Fourier transform infrared spectroscopy revealed spherical nanoparticles without aggregation, with the drugs molecularly dis- persed within the lipid matrix. Both STP and CBD showed sustained release profiles and demonstrated oral pharmacokinetic profiles that were comparable or superior to current commercial products. Conclusions: This novel formulation represents a promising thera- peutic alternative for DS, enabling the co-administration of STP and CBD while potentially enhancing CBD bioavailability and treatment adherence in pediatric populations.Laboratorio de Investigación y Desarrollo de Bioactivos2026info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionArticulohttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfhttp://sedici.unlp.edu.ar/handle/10915/195987enginfo:eu-repo/semantics/altIdentifier/issn/1999-4923info:eu-repo/semantics/altIdentifier/doi/10.3390/pharmaceutics18040503info:eu-repo/semantics/openAccesshttp://creativecommons.org/licenses/by/4.0/Creative Commons Attribution 4.0 International (CC BY 4.0)reponame:SEDICI (UNLP)instname:Universidad Nacional de La Platainstacron:UNLP2026-06-23T11:17:12Zoai:sedici.unlp.edu.ar:10915/195987Institucionalhttp://sedici.unlp.edu.ar/Universidad públicaNo correspondehttp://sedici.unlp.edu.ar/oai/snrdalira@sedici.unlp.edu.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:13292026-06-23 11:17:13.049SEDICI (UNLP) - Universidad Nacional de La Platafalse
dc.title.none.fl_str_mv Lipid Nanoparticles with Stiripentol and Cannabidiol Oil: From Rational Optimization to Preclinical Characterization
title Lipid Nanoparticles with Stiripentol and Cannabidiol Oil: From Rational Optimization to Preclinical Characterization
spellingShingle Lipid Nanoparticles with Stiripentol and Cannabidiol Oil: From Rational Optimization to Preclinical Characterization
Scioli Montoto, Sebastián
Bioquímica
Cannabidiol
Dravet syndrome
Lipid nanoparticles
Nanostructured lipid carriers
Oral administration
Pediatric formulations
Pharmacokinetic study
Release profile
Response surface
Stiripentol
title_short Lipid Nanoparticles with Stiripentol and Cannabidiol Oil: From Rational Optimization to Preclinical Characterization
title_full Lipid Nanoparticles with Stiripentol and Cannabidiol Oil: From Rational Optimization to Preclinical Characterization
title_fullStr Lipid Nanoparticles with Stiripentol and Cannabidiol Oil: From Rational Optimization to Preclinical Characterization
title_full_unstemmed Lipid Nanoparticles with Stiripentol and Cannabidiol Oil: From Rational Optimization to Preclinical Characterization
title_sort Lipid Nanoparticles with Stiripentol and Cannabidiol Oil: From Rational Optimization to Preclinical Characterization
dc.creator.none.fl_str_mv Scioli Montoto, Sebastián
Lobos, Martín
Melis, Mauricio Ezequiel
Ruatta, Santiago
Muraca, Giuliana
Chain, Cecilia Yamil
Cisneros, José Sebastián
Álvarez, Vera Alejandra
Islan, Germán Abel
Talevi, Alan
Ruiz, María Esperanza
author Scioli Montoto, Sebastián
author_facet Scioli Montoto, Sebastián
Lobos, Martín
Melis, Mauricio Ezequiel
Ruatta, Santiago
Muraca, Giuliana
Chain, Cecilia Yamil
Cisneros, José Sebastián
Álvarez, Vera Alejandra
Islan, Germán Abel
Talevi, Alan
Ruiz, María Esperanza
author_role author
author2 Lobos, Martín
Melis, Mauricio Ezequiel
Ruatta, Santiago
Muraca, Giuliana
Chain, Cecilia Yamil
Cisneros, José Sebastián
Álvarez, Vera Alejandra
Islan, Germán Abel
Talevi, Alan
Ruiz, María Esperanza
author2_role author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Bioquímica
Cannabidiol
Dravet syndrome
Lipid nanoparticles
Nanostructured lipid carriers
Oral administration
Pediatric formulations
Pharmacokinetic study
Release profile
Response surface
Stiripentol
topic Bioquímica
Cannabidiol
Dravet syndrome
Lipid nanoparticles
Nanostructured lipid carriers
Oral administration
Pediatric formulations
Pharmacokinetic study
Release profile
Response surface
Stiripentol
dc.description.none.fl_txt_mv Background/Objectives: Dravet Syndrome (DS) is a severe form of epilepsy that typically manifests in the first year of life and often requires polytherapy with two or more anti- seizure medications (ASMs) to achieve adequate seizure control. Whereas the combination of stiripentol (STP) and cannabidiol (CBD) has demonstrated clinical efficacy, it presents significant formulation challenges due to the low aqueous solubility and poor oral bioavail- ability of both compounds. Furthermore, the high daily dosages of STP (approximately 50 mg/kg/day or higher) and the oily nature of conventional CBD formulations often hinder patient compliance, as pediatric patients frequently reject these treatments due to unfavorable organoleptic properties. Methods: Nanostructured lipid carriers (NLCs) con- taining STP and CBD suspended in an aqueous medium were developed. The formulation was optimized using Response Surface Methodology (RSM) and subjected to comprehen- sive in vitro and in vivo characterization. Results: The optimized formulation exhibited a mean particle size of 175.3 nm, a polydispersity index (PDI) of 0.232, a zeta potential of −8.35 mV, and an encapsulation efficiency greater than 99% for both drugs. Physico- chemical characterization via atomic force microscopy, differential scanning calorimetry, thermogravimetric analysis, X-ray diffraction, and Fourier transform infrared spectroscopy revealed spherical nanoparticles without aggregation, with the drugs molecularly dis- persed within the lipid matrix. Both STP and CBD showed sustained release profiles and demonstrated oral pharmacokinetic profiles that were comparable or superior to current commercial products. Conclusions: This novel formulation represents a promising thera- peutic alternative for DS, enabling the co-administration of STP and CBD while potentially enhancing CBD bioavailability and treatment adherence in pediatric populations.
Laboratorio de Investigación y Desarrollo de Bioactivos
description Background/Objectives: Dravet Syndrome (DS) is a severe form of epilepsy that typically manifests in the first year of life and often requires polytherapy with two or more anti- seizure medications (ASMs) to achieve adequate seizure control. Whereas the combination of stiripentol (STP) and cannabidiol (CBD) has demonstrated clinical efficacy, it presents significant formulation challenges due to the low aqueous solubility and poor oral bioavail- ability of both compounds. Furthermore, the high daily dosages of STP (approximately 50 mg/kg/day or higher) and the oily nature of conventional CBD formulations often hinder patient compliance, as pediatric patients frequently reject these treatments due to unfavorable organoleptic properties. Methods: Nanostructured lipid carriers (NLCs) con- taining STP and CBD suspended in an aqueous medium were developed. The formulation was optimized using Response Surface Methodology (RSM) and subjected to comprehen- sive in vitro and in vivo characterization. Results: The optimized formulation exhibited a mean particle size of 175.3 nm, a polydispersity index (PDI) of 0.232, a zeta potential of −8.35 mV, and an encapsulation efficiency greater than 99% for both drugs. Physico- chemical characterization via atomic force microscopy, differential scanning calorimetry, thermogravimetric analysis, X-ray diffraction, and Fourier transform infrared spectroscopy revealed spherical nanoparticles without aggregation, with the drugs molecularly dis- persed within the lipid matrix. Both STP and CBD showed sustained release profiles and demonstrated oral pharmacokinetic profiles that were comparable or superior to current commercial products. Conclusions: This novel formulation represents a promising thera- peutic alternative for DS, enabling the co-administration of STP and CBD while potentially enhancing CBD bioavailability and treatment adherence in pediatric populations.
publishDate 2026
dc.date.none.fl_str_mv 2026
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
Articulo
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://sedici.unlp.edu.ar/handle/10915/195987
url http://sedici.unlp.edu.ar/handle/10915/195987
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/issn/1999-4923
info:eu-repo/semantics/altIdentifier/doi/10.3390/pharmaceutics18040503
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
http://creativecommons.org/licenses/by/4.0/
Creative Commons Attribution 4.0 International (CC BY 4.0)
eu_rights_str_mv openAccess
rights_invalid_str_mv http://creativecommons.org/licenses/by/4.0/
Creative Commons Attribution 4.0 International (CC BY 4.0)
dc.format.none.fl_str_mv application/pdf
dc.source.none.fl_str_mv reponame:SEDICI (UNLP)
instname:Universidad Nacional de La Plata
instacron:UNLP
reponame_str SEDICI (UNLP)
collection SEDICI (UNLP)
instname_str Universidad Nacional de La Plata
instacron_str UNLP
institution UNLP
repository.name.fl_str_mv SEDICI (UNLP) - Universidad Nacional de La Plata
repository.mail.fl_str_mv alira@sedici.unlp.edu.ar
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score 13.24418

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