Drug delivery applications of hydrophobic deep eutectic solvent-in-water nanoemulsions: A comparative analysis of ultrasound emulsification and membrane-assisted nanoemulsification

The emergence of green chemistry and engineering principles to enforce sustainability aspects has ensured the prevalence of green solvents and green processes. Our study addresses this quest by exploring drug delivery applications of hydrophobic deep eutectic solvents (DESs) which are alternative gr...

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Autores: Syed, Usman T., Calzada-Funes, Javier, Mendoza, Gracia, Arruebo, Manuel, Piacentini, Emma, Giorno, Lidietta, Crespo, João G., Brazinha, Carla, Sebastián, Víctor
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2025
País:España
Institución:Consejo Superior de Investigaciones Científicas (CSIC)
Repositorio:DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:oai:digital.csic.es:10261/389794
Acceso en línea:http://hdl.handle.net/10261/389794
Access Level:acceso abierto
Palabra clave:Deep eutectic solvent
Lidocaine
Membrane emulsification
Cytotoxicity
Nanoemulsions
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network_name_str España
repository_id_str
dc.title.none.fl_str_mv Drug delivery applications of hydrophobic deep eutectic solvent-in-water nanoemulsions: A comparative analysis of ultrasound emulsification and membrane-assisted nanoemulsification
title Drug delivery applications of hydrophobic deep eutectic solvent-in-water nanoemulsions: A comparative analysis of ultrasound emulsification and membrane-assisted nanoemulsification
spellingShingle Drug delivery applications of hydrophobic deep eutectic solvent-in-water nanoemulsions: A comparative analysis of ultrasound emulsification and membrane-assisted nanoemulsification
Syed, Usman T.
Deep eutectic solvent
Lidocaine
Membrane emulsification
Cytotoxicity
Nanoemulsions
title_short Drug delivery applications of hydrophobic deep eutectic solvent-in-water nanoemulsions: A comparative analysis of ultrasound emulsification and membrane-assisted nanoemulsification
title_full Drug delivery applications of hydrophobic deep eutectic solvent-in-water nanoemulsions: A comparative analysis of ultrasound emulsification and membrane-assisted nanoemulsification
title_fullStr Drug delivery applications of hydrophobic deep eutectic solvent-in-water nanoemulsions: A comparative analysis of ultrasound emulsification and membrane-assisted nanoemulsification
title_full_unstemmed Drug delivery applications of hydrophobic deep eutectic solvent-in-water nanoemulsions: A comparative analysis of ultrasound emulsification and membrane-assisted nanoemulsification
title_sort Drug delivery applications of hydrophobic deep eutectic solvent-in-water nanoemulsions: A comparative analysis of ultrasound emulsification and membrane-assisted nanoemulsification
dc.creator.none.fl_str_mv Syed, Usman T.
Calzada-Funes, Javier
Mendoza, Gracia
Arruebo, Manuel
Piacentini, Emma
Giorno, Lidietta
Crespo, João G.
Brazinha, Carla
Sebastián, Víctor
author Syed, Usman T.
author_facet Syed, Usman T.
Calzada-Funes, Javier
Mendoza, Gracia
Arruebo, Manuel
Piacentini, Emma
Giorno, Lidietta
Crespo, João G.
Brazinha, Carla
Sebastián, Víctor
author_role author
author2 Calzada-Funes, Javier
Mendoza, Gracia
Arruebo, Manuel
Piacentini, Emma
Giorno, Lidietta
Crespo, João G.
Brazinha, Carla
Sebastián, Víctor
author2_role author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Agencia Estatal de Investigación (España)
Ministerio de Ciencia, Innovación y Universidades (España)
European Commission
Ministério da Ciência, Tecnologia e Ensino Superior (Portugal)
Fundação para a Ciência e a Tecnologia (Portugal)
Instituto de Salud Carlos III
Centre National de la Recherche Scientifique (France)
Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]
dc.subject.none.fl_str_mv Deep eutectic solvent
Lidocaine
Membrane emulsification
Cytotoxicity
Nanoemulsions
topic Deep eutectic solvent
Lidocaine
Membrane emulsification
Cytotoxicity
Nanoemulsions
description The emergence of green chemistry and engineering principles to enforce sustainability aspects has ensured the prevalence of green solvents and green processes. Our study addresses this quest by exploring drug delivery applications of hydrophobic deep eutectic solvents (DESs) which are alternative green solvents. Initially, this work showcases the hydrophobic drug solubilization capabilities of a natural hydrophobic DES, menthol, and decanoic acid. To consider biomedical applications wherein polar media are encountered, this work further demonstrates the potential drug delivery application of these systems by encapsulating the anti-inflammatory local anesthetic lidocaine in hydrophobic DES-in-water nanoemulsions. NMR studies confirm the high solubility of the hydrophobic drug in hydrophobic DES comprising menthol and decanoic acid (1:2 molar ratio). Ultrasound emulsification and energy-efficient membrane emulsification techniques were employed to disperse 4% (v/v) DES into a 2% (w/w) Tween 20 surfactant aqueous solution. An isoporous microengineered membrane (nominal pore size ∼ 9 μm) was used to produce lidocaine-loaded DES-based nanoemulsions. Such membrane-assisted nanoemulsification was possible because the hydrophobic DES exhibits relatively low interfacial tension with the continuous phase and acts as a cosurfactant. Moreover, increased concentrations of lidocaine within the DES resulted in a further decrease in the interfacial tension and a lower melting point. Among the kinetic models analyzed to evaluate the release of lidocaine encapsulated in hydrophobic DES-in-water nanoemulsions, the Korsmeyer-Peppas kinetic model provided the best fit. The release constant "n" of <0.5 indicates that the drug release mechanism is predominantly governed by diffusion. Additionally, cytotoxicity against various human cell lines demonstrated the nanoemulsion's potential for anti-inflammatory drug delivery applications. Consequently, the nanoemulsion of DES presents a promising solution for the effective loading and delivery of poorly soluble drugs. This innovative approach enhances drug solubility and bioavailability, providing a versatile platform for controlled drug release. By leveraging the advantages of nanoemulsion technology, our study underscores the potential of DES-based formulations to promote drug delivery systems across a variety of therapeutic applications.
publishDate 2025
dc.date.none.fl_str_mv 2025
2025
2025
dc.type.none.fl_str_mv info:eu-repo/semantics/article
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Publisher's version
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/10261/389794
url http://hdl.handle.net/10261/389794
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
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info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2021-2023/PID2021-127847OB-I00
info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2021-2023/PDC2022-133866-I00
info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2021-2023/CEX2023-001286-S
Syed, Usman T.; Calzada-Funes, Javier ; Mendoza, Gracia; Arruebo, Manuel; Piacentini, Emma; Giorno, Lidietta; Crespo, João G.; Brazinha, Carla; Sebastián, Víctor; 2025; Supporting Information: Drug delivery applications of hydrophobic deep eutectic solvent-in-water nanoemulsions: A comparative analysis of ultrasound emulsification and membrane-assisted nanoemulsification [Dataset]; American Chemical Society; https://doi.org/10.1021/acsami.4c13163
https://doi.org/10.1021/acsami.4c13163
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dc.publisher.none.fl_str_mv American Chemical Society
publisher.none.fl_str_mv American Chemical Society
dc.source.none.fl_str_mv reponame:DIGITAL.CSIC. Repositorio Institucional del CSIC
instname:Consejo Superior de Investigaciones Científicas (CSIC)
instname_str Consejo Superior de Investigaciones Científicas (CSIC)
reponame_str DIGITAL.CSIC. Repositorio Institucional del CSIC
collection DIGITAL.CSIC. Repositorio Institucional del CSIC
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spelling Drug delivery applications of hydrophobic deep eutectic solvent-in-water nanoemulsions: A comparative analysis of ultrasound emulsification and membrane-assisted nanoemulsificationSyed, Usman T.Calzada-Funes, JavierMendoza, GraciaArruebo, ManuelPiacentini, EmmaGiorno, LidiettaCrespo, João G.Brazinha, CarlaSebastián, VíctorDeep eutectic solventLidocaineMembrane emulsificationCytotoxicityNanoemulsionsThe emergence of green chemistry and engineering principles to enforce sustainability aspects has ensured the prevalence of green solvents and green processes. Our study addresses this quest by exploring drug delivery applications of hydrophobic deep eutectic solvents (DESs) which are alternative green solvents. Initially, this work showcases the hydrophobic drug solubilization capabilities of a natural hydrophobic DES, menthol, and decanoic acid. To consider biomedical applications wherein polar media are encountered, this work further demonstrates the potential drug delivery application of these systems by encapsulating the anti-inflammatory local anesthetic lidocaine in hydrophobic DES-in-water nanoemulsions. NMR studies confirm the high solubility of the hydrophobic drug in hydrophobic DES comprising menthol and decanoic acid (1:2 molar ratio). Ultrasound emulsification and energy-efficient membrane emulsification techniques were employed to disperse 4% (v/v) DES into a 2% (w/w) Tween 20 surfactant aqueous solution. An isoporous microengineered membrane (nominal pore size ∼ 9 μm) was used to produce lidocaine-loaded DES-based nanoemulsions. Such membrane-assisted nanoemulsification was possible because the hydrophobic DES exhibits relatively low interfacial tension with the continuous phase and acts as a cosurfactant. Moreover, increased concentrations of lidocaine within the DES resulted in a further decrease in the interfacial tension and a lower melting point. Among the kinetic models analyzed to evaluate the release of lidocaine encapsulated in hydrophobic DES-in-water nanoemulsions, the Korsmeyer-Peppas kinetic model provided the best fit. The release constant "n" of <0.5 indicates that the drug release mechanism is predominantly governed by diffusion. Additionally, cytotoxicity against various human cell lines demonstrated the nanoemulsion's potential for anti-inflammatory drug delivery applications. Consequently, the nanoemulsion of DES presents a promising solution for the effective loading and delivery of poorly soluble drugs. This innovative approach enhances drug solubility and bioavailability, providing a versatile platform for controlled drug release. By leveraging the advantages of nanoemulsion technology, our study underscores the potential of DES-based formulations to promote drug delivery systems across a variety of therapeutic applications.The authors would like to acknowledge the Executive Agency for Education, Audiovisual, and Culture (EACEA) of the European Commission for the scholarship grant of Erasmus Mundus Doctorate in Membrane Engineering (EUDIME) program to Syed Usman Taqui. Prof. Reyes Mallada and Dr. Ruth Lahoz from the Nanoscience Institute of Aragon (INA), University of Zaragoza, are acknowledged for their unconditional support in fabrication and characterization of metallic membranes. This work was also supported by the Associate Laboratory for Green Chemistry-LAQV which is financed by national funds from FCT/MCTES (UIDB/50006/2020). V.S. acknowledges the financial support by the Spanish Ministry of Science and Innovation (grant no. PID2021-127847OB-I00). We also acknowledge the financial support of the NextGenerationEU/PRTR thanks to the project: PDC2022-133866-I00. CIBER-BBN is an initiative funded by the VI National R&D&i Plan 2008–2011, Iniciativa Ingenio 2010, Consolider Program. G.M. gratefully acknowledges the support from the Miguel Servet Program (MS19/00092; Instituto de Salud Carlos III). INMA researchers thank the Severo Ochoa Grant CEX2023-001286-S funded by MICIU/ AEI/10.13039/501100011033. Authors thank the “Advanced Microscopy Laboratory” ELECMI and NANBIOSIS ICTSs, for access to their instruments. Part of the work was supported within the Bio4Mem project (CNR-DCM.AD006.234).With funding from the Spanish government through the "Severo Ochoa Centre of Excellence" accreditation (CEX2023-001286-S).Peer reviewedAmerican Chemical SocietyAgencia Estatal de Investigación (España)Ministerio de Ciencia, Innovación y Universidades (España)European CommissionMinistério da Ciência, Tecnologia e Ensino Superior (Portugal)Fundação para a Ciência e a Tecnologia (Portugal)Instituto de Salud Carlos IIICentre National de la Recherche Scientifique (France)Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]202520252025info:eu-repo/semantics/articlehttp://purl.org/coar/resource_type/c_6501Publisher's versioninfo:eu-repo/semantics/publishedVersionapplication/pdfhttp://hdl.handle.net/10261/389794reponame:DIGITAL.CSIC. Repositorio Institucional del CSICinstname:Consejo Superior de Investigaciones Científicas (CSIC)Inglés#PLACEHOLDER_PARENT_METADATA_VALUE##PLACEHOLDER_PARENT_METADATA_VALUE##PLACEHOLDER_PARENT_METADATA_VALUE#info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2021-2023/PID2021-127847OB-I00info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2021-2023/PDC2022-133866-I00info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2021-2023/CEX2023-001286-SSyed, Usman T.; Calzada-Funes, Javier ; Mendoza, Gracia; Arruebo, Manuel; Piacentini, Emma; Giorno, Lidietta; Crespo, João G.; Brazinha, Carla; Sebastián, Víctor; 2025; Supporting Information: Drug delivery applications of hydrophobic deep eutectic solvent-in-water nanoemulsions: A comparative analysis of ultrasound emulsification and membrane-assisted nanoemulsification [Dataset]; American Chemical Society; https://doi.org/10.1021/acsami.4c13163https://doi.org/10.1021/acsami.4c13163Síinfo:eu-repo/semantics/openAccessoai:digital.csic.es:10261/3897942026-05-22T06:33:51Z
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