The role of counterions in the membrane-disruptive properties of pH-sensitive lysine-based surfactants

Surfactants are among the most versatile and widely used excipients in pharmaceuticals. This versatility, together with their pH-responsive membrane-disruptive activity and low toxicity, could also enable their potential application in drug delivery systems. Five anionic lysine-based surfactants whi...

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Autores: Nogueira, Daniele Rubert, Mitjans, Montserrat, Infante, María Rosa, Vinardell, M. Pilar
Tipo de recurso: artículo
Estado:Versión aceptada para publicación
Fecha de publicación:2011
País:España
Institución:Consejo Superior de Investigaciones Científicas (CSIC)
Repositorio:DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:oai:digital.csic.es:10261/332880
Acceso en línea:http://hdl.handle.net/10261/332880
https://api.elsevier.com/content/abstract/scopus_id/79957668944
Access Level:acceso abierto
Palabra clave:Cytotoxicity
Drug delivery
Hemolysis
Membrane disruption
pH-sensitivity
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spelling The role of counterions in the membrane-disruptive properties of pH-sensitive lysine-based surfactantsNogueira, Daniele RubertMitjans, MontserratInfante, María RosaVinardell, M. PilarCytotoxicityDrug deliveryHemolysisMembrane disruptionpH-sensitivitySurfactants are among the most versatile and widely used excipients in pharmaceuticals. This versatility, together with their pH-responsive membrane-disruptive activity and low toxicity, could also enable their potential application in drug delivery systems. Five anionic lysine-based surfactants which differ in the nature of their counterion were studied. Their capacity to disrupt the cell membrane was examined under a range of pH values, concentrations and incubation times, using a standard hemolysis assay as a model for endosomal membranes. The surfactants showed pH-sensitive hemolytic activity and improved kinetics at the endosomal pH range. Low concentrations resulted in negligible hemolysis at physiological pH and high membrane lytic activity at pH 5.4, which is in the range characteristic of late endosomes. With increasing concentration, the surfactants showed an enhanced capacity to lyse cell membranes, and also caused significant membrane disruption at physiological pH. This observation indicates that, at high concentrations, surfactant behavior is independent of pH. The mechanism of surfactant-mediated membrane destabilization was addressed, and scanning electron microscopy studies were also performed to evaluate the effects of the compounds on erythrocyte morphology as a function of pH. The in vitro cytotoxicity of the surfactants was assessed by MTT and NRU assays with the 3T3 cell line. The influence of different types of counterion on hemolytic activity and the potential applications of these surfactants in drug delivery are discussed. The possibility of using pH-sensitive surfactants for endosome disruption could hold great promise for intracellular drug delivery systems in future therapeutic applications.This research was supported by Project CTQ2009-14151-C02-02 from Ministerio de Ciencia e Innovación (Spain). D.R. Nogueira holds a doctoral grant from MAEC-AECID (Spain).Peer reviewedElsevierComisión Asesora de Investigación Científica y Técnica, CAICYT (España)Ministerio de Asuntos Exteriores y Cooperación (España)Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]202320232011info:eu-repo/semantics/articlehttp://purl.org/coar/resource_type/c_6501Postprintinfo:eu-repo/semantics/acceptedVersionapplication/pdfhttp://hdl.handle.net/10261/332880https://api.elsevier.com/content/abstract/scopus_id/79957668944reponame:DIGITAL.CSIC. Repositorio Institucional del CSICinstname:Consejo Superior de Investigaciones Científicas (CSIC)Ingléshttps://doi.org/10.1016/j.actbio.2011.03.017Síinfo:eu-repo/semantics/openAccessoai:digital.csic.es:10261/3328802026-05-22T06:33:51Z
dc.title.none.fl_str_mv The role of counterions in the membrane-disruptive properties of pH-sensitive lysine-based surfactants
title The role of counterions in the membrane-disruptive properties of pH-sensitive lysine-based surfactants
spellingShingle The role of counterions in the membrane-disruptive properties of pH-sensitive lysine-based surfactants
Nogueira, Daniele Rubert
Cytotoxicity
Drug delivery
Hemolysis
Membrane disruption
pH-sensitivity
title_short The role of counterions in the membrane-disruptive properties of pH-sensitive lysine-based surfactants
title_full The role of counterions in the membrane-disruptive properties of pH-sensitive lysine-based surfactants
title_fullStr The role of counterions in the membrane-disruptive properties of pH-sensitive lysine-based surfactants
title_full_unstemmed The role of counterions in the membrane-disruptive properties of pH-sensitive lysine-based surfactants
title_sort The role of counterions in the membrane-disruptive properties of pH-sensitive lysine-based surfactants
dc.creator.none.fl_str_mv Nogueira, Daniele Rubert
Mitjans, Montserrat
Infante, María Rosa
Vinardell, M. Pilar
author Nogueira, Daniele Rubert
author_facet Nogueira, Daniele Rubert
Mitjans, Montserrat
Infante, María Rosa
Vinardell, M. Pilar
author_role author
author2 Mitjans, Montserrat
Infante, María Rosa
Vinardell, M. Pilar
author2_role author
author
author
dc.contributor.none.fl_str_mv Comisión Asesora de Investigación Científica y Técnica, CAICYT (España)
Ministerio de Asuntos Exteriores y Cooperación (España)
Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]
dc.subject.none.fl_str_mv Cytotoxicity
Drug delivery
Hemolysis
Membrane disruption
pH-sensitivity
topic Cytotoxicity
Drug delivery
Hemolysis
Membrane disruption
pH-sensitivity
description Surfactants are among the most versatile and widely used excipients in pharmaceuticals. This versatility, together with their pH-responsive membrane-disruptive activity and low toxicity, could also enable their potential application in drug delivery systems. Five anionic lysine-based surfactants which differ in the nature of their counterion were studied. Their capacity to disrupt the cell membrane was examined under a range of pH values, concentrations and incubation times, using a standard hemolysis assay as a model for endosomal membranes. The surfactants showed pH-sensitive hemolytic activity and improved kinetics at the endosomal pH range. Low concentrations resulted in negligible hemolysis at physiological pH and high membrane lytic activity at pH 5.4, which is in the range characteristic of late endosomes. With increasing concentration, the surfactants showed an enhanced capacity to lyse cell membranes, and also caused significant membrane disruption at physiological pH. This observation indicates that, at high concentrations, surfactant behavior is independent of pH. The mechanism of surfactant-mediated membrane destabilization was addressed, and scanning electron microscopy studies were also performed to evaluate the effects of the compounds on erythrocyte morphology as a function of pH. The in vitro cytotoxicity of the surfactants was assessed by MTT and NRU assays with the 3T3 cell line. The influence of different types of counterion on hemolytic activity and the potential applications of these surfactants in drug delivery are discussed. The possibility of using pH-sensitive surfactants for endosome disruption could hold great promise for intracellular drug delivery systems in future therapeutic applications.
publishDate 2011
dc.date.none.fl_str_mv 2011
2023
2023
dc.type.none.fl_str_mv info:eu-repo/semantics/article
http://purl.org/coar/resource_type/c_6501
Postprint
info:eu-repo/semantics/acceptedVersion
format article
status_str acceptedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/10261/332880
https://api.elsevier.com/content/abstract/scopus_id/79957668944
url http://hdl.handle.net/10261/332880
https://api.elsevier.com/content/abstract/scopus_id/79957668944
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv https://doi.org/10.1016/j.actbio.2011.03.017
Sí
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Elsevier
publisher.none.fl_str_mv Elsevier
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
repository.name.fl_str_mv
repository.mail.fl_str_mv
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