Molecular Dynamics Study on the Encapsulation of Prilocaine in Liposomes at Physiological pH

Autores
Giupponi, Giovanni; Martini, María Florencia; Pickholz, Mónica Andrea
Año de publicación
2013
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
In this work, we investigated the concentration effects on the encapsulation of prilocaine (PLC), an aminoamide local anesthetic, into a small unilamellar liposome, at physiological pH. On the line of our previous work, we have carried out Molecular Dynamics (MD) simulations using a coarse grain (CG) model that allow us to reach the microsecond time scale. At physiological pH there is a partition between protonated and neutral PLCs. In order to estimate the protonated/neutral PLC ratio at physiological pH (7.4), we have used the Henderson-Hasselbach equation. We have studied three PLC:lipid molar concentrations, ranging between 10:10 to 1:4. We essentially found that all neutral PLC molecules rapidly diffuse into the hydrophobic region of the vesicle adopting an asymmetric bimodal distribution. Moreover, protonated PLC molecules partition between the external monolayer of the vesicle and the water phase, having a high rate of exchange between this two phases, with no access to the inner part of the liposome in a concentration dependent way. In this way, we found that the behavior of PLCs at physiological pH is a combination of high and low pH, especially at low concentration of local anesthetics.
Fil: Giupponi, Giovanni. Universidad de Barcelona. Facultad de Física; España;
Fil: Martini, María Florencia. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Tecnología Farmacéutica; Argentina; Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; Argentina;
Fil: Pickholz, Mónica Andrea. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Tecnología Farmacéutica; Argentina; Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; Argentina;
Materia
Coarse Grain
Local Anesthetics
Liposome
Molecular Dynamics
Prilocaine
Physiological Ph
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/1862
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/1862
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Molecular Dynamics Study on the Encapsulation of Prilocaine in Liposomes at Physiological pHGiupponi, GiovanniMartini, María FlorenciaPickholz, Mónica AndreaCoarse GrainLocal AnestheticsLiposomeMolecular DynamicsPrilocainePhysiological Phhttps://purl.org/becyt/ford/1.4https://purl.org/becyt/ford/1https://purl.org/becyt/ford/3.2https://purl.org/becyt/ford/3In this work, we investigated the concentration effects on the encapsulation of prilocaine (PLC), an aminoamide local anesthetic, into a small unilamellar liposome, at physiological pH. On the line of our previous work, we have carried out Molecular Dynamics (MD) simulations using a coarse grain (CG) model that allow us to reach the microsecond time scale. At physiological pH there is a partition between protonated and neutral PLCs. In order to estimate the protonated/neutral PLC ratio at physiological pH (7.4), we have used the Henderson-Hasselbach equation. We have studied three PLC:lipid molar concentrations, ranging between 10:10 to 1:4. We essentially found that all neutral PLC molecules rapidly diffuse into the hydrophobic region of the vesicle adopting an asymmetric bimodal distribution. Moreover, protonated PLC molecules partition between the external monolayer of the vesicle and the water phase, having a high rate of exchange between this two phases, with no access to the inner part of the liposome in a concentration dependent way. In this way, we found that the behavior of PLCs at physiological pH is a combination of high and low pH, especially at low concentration of local anesthetics.Fil: Giupponi, Giovanni. Universidad de Barcelona. Facultad de Física; España;Fil: Martini, María Florencia. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Tecnología Farmacéutica; Argentina; Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; Argentina;Fil: Pickholz, Mónica Andrea. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Tecnología Farmacéutica; Argentina; Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; Argentina;American Scientific Publishers2013-02info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/1862Giupponi, Giovanni; Martini, María Florencia; Pickholz, Mónica Andrea; Molecular Dynamics Study on the Encapsulation of Prilocaine in Liposomes at Physiological pH; American Scientific Publishers; Journal of Biomaterials and Tissue Engineering; 3; 1; 2-2013; 141-1472157-9083enginfo:eu-repo/semantics/altIdentifier/url/http://www.ingentaconnect.com/content/asp/jbte/2013/00000003/00000001/art00011?token=004f15169b7117e41225f4038592c4941287678463e4551576b34272c5f7b3d6d3f4e4b34328e38info:eu-repo/semantics/altIdentifier/doi/10.1166/jbt.2013.1074info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-10T13:08:21Zoai:ri.conicet.gov.ar:11336/1862instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-09-10 13:08:21.205CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Molecular Dynamics Study on the Encapsulation of Prilocaine in Liposomes at Physiological pH
title Molecular Dynamics Study on the Encapsulation of Prilocaine in Liposomes at Physiological pH
spellingShingle Molecular Dynamics Study on the Encapsulation of Prilocaine in Liposomes at Physiological pH
Giupponi, Giovanni
Coarse Grain
Local Anesthetics
Liposome
Molecular Dynamics
Prilocaine
Physiological Ph
title_short Molecular Dynamics Study on the Encapsulation of Prilocaine in Liposomes at Physiological pH
title_full Molecular Dynamics Study on the Encapsulation of Prilocaine in Liposomes at Physiological pH
title_fullStr Molecular Dynamics Study on the Encapsulation of Prilocaine in Liposomes at Physiological pH
title_full_unstemmed Molecular Dynamics Study on the Encapsulation of Prilocaine in Liposomes at Physiological pH
title_sort Molecular Dynamics Study on the Encapsulation of Prilocaine in Liposomes at Physiological pH
dc.creator.none.fl_str_mv Giupponi, Giovanni
Martini, María Florencia
Pickholz, Mónica Andrea
author Giupponi, Giovanni
author_facet Giupponi, Giovanni
Martini, María Florencia
Pickholz, Mónica Andrea
author_role author
author2 Martini, María Florencia
Pickholz, Mónica Andrea
author2_role author
author
dc.subject.none.fl_str_mv Coarse Grain
Local Anesthetics
Liposome
Molecular Dynamics
Prilocaine
Physiological Ph
topic Coarse Grain
Local Anesthetics
Liposome
Molecular Dynamics
Prilocaine
Physiological Ph
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.4
https://purl.org/becyt/ford/1
https://purl.org/becyt/ford/3.2
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv In this work, we investigated the concentration effects on the encapsulation of prilocaine (PLC), an aminoamide local anesthetic, into a small unilamellar liposome, at physiological pH. On the line of our previous work, we have carried out Molecular Dynamics (MD) simulations using a coarse grain (CG) model that allow us to reach the microsecond time scale. At physiological pH there is a partition between protonated and neutral PLCs. In order to estimate the protonated/neutral PLC ratio at physiological pH (7.4), we have used the Henderson-Hasselbach equation. We have studied three PLC:lipid molar concentrations, ranging between 10:10 to 1:4. We essentially found that all neutral PLC molecules rapidly diffuse into the hydrophobic region of the vesicle adopting an asymmetric bimodal distribution. Moreover, protonated PLC molecules partition between the external monolayer of the vesicle and the water phase, having a high rate of exchange between this two phases, with no access to the inner part of the liposome in a concentration dependent way. In this way, we found that the behavior of PLCs at physiological pH is a combination of high and low pH, especially at low concentration of local anesthetics.
Fil: Giupponi, Giovanni. Universidad de Barcelona. Facultad de Física; España;
Fil: Martini, María Florencia. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Tecnología Farmacéutica; Argentina; Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; Argentina;
Fil: Pickholz, Mónica Andrea. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Tecnología Farmacéutica; Argentina; Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; Argentina;
description In this work, we investigated the concentration effects on the encapsulation of prilocaine (PLC), an aminoamide local anesthetic, into a small unilamellar liposome, at physiological pH. On the line of our previous work, we have carried out Molecular Dynamics (MD) simulations using a coarse grain (CG) model that allow us to reach the microsecond time scale. At physiological pH there is a partition between protonated and neutral PLCs. In order to estimate the protonated/neutral PLC ratio at physiological pH (7.4), we have used the Henderson-Hasselbach equation. We have studied three PLC:lipid molar concentrations, ranging between 10:10 to 1:4. We essentially found that all neutral PLC molecules rapidly diffuse into the hydrophobic region of the vesicle adopting an asymmetric bimodal distribution. Moreover, protonated PLC molecules partition between the external monolayer of the vesicle and the water phase, having a high rate of exchange between this two phases, with no access to the inner part of the liposome in a concentration dependent way. In this way, we found that the behavior of PLCs at physiological pH is a combination of high and low pH, especially at low concentration of local anesthetics.
publishDate 2013
dc.date.none.fl_str_mv 2013-02
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
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://hdl.handle.net/11336/1862
Giupponi, Giovanni; Martini, María Florencia; Pickholz, Mónica Andrea; Molecular Dynamics Study on the Encapsulation of Prilocaine in Liposomes at Physiological pH; American Scientific Publishers; Journal of Biomaterials and Tissue Engineering; 3; 1; 2-2013; 141-147
2157-9083
url http://hdl.handle.net/11336/1862
identifier_str_mv Giupponi, Giovanni; Martini, María Florencia; Pickholz, Mónica Andrea; Molecular Dynamics Study on the Encapsulation of Prilocaine in Liposomes at Physiological pH; American Scientific Publishers; Journal of Biomaterials and Tissue Engineering; 3; 1; 2-2013; 141-147
2157-9083
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/http://www.ingentaconnect.com/content/asp/jbte/2013/00000003/00000001/art00011?token=004f15169b7117e41225f4038592c4941287678463e4551576b34272c5f7b3d6d3f4e4b34328e38
info:eu-repo/semantics/altIdentifier/doi/10.1166/jbt.2013.1074
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv American Scientific Publishers
publisher.none.fl_str_mv American Scientific Publishers
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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score 12.993085

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