Cholesterol nanoarchaeosomes for alendronate targeted delivery as an anti-endothelial dysfunction agent

Autores
Jerez, Horacio Emanuel; Simioni, Yamila Roxana; Ghosal, Kajal; Morilla, María José; Romero, Eder Lilia
Año de publicación
2024
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Sodium alendronate (ALN) is a very hydrosoluble and poorly permeable molecule used as an antiresorptive agent and with vascularanticalcifying capacity. Loaded into targeted nanovesicles, its anti-inflammatory activity may be amplified towards extra-osseousand noncalcified target cells, such as severely irritated vascular endothelium. Here cytotoxicity, mitochondrial membrane potential,ATP content, and membrane fluidity of human endothelial venous cells (HUVECs) were determined after endocytosis of ALNloadednanoarchaeosomes (nanoARC-Chol(ALN), made of polar lipids from Halorubrum tebenquichense: cholesterol 7:3 w/w,166 ± 5 nm, 0.16 ± 0.02 PDI, −40.8 ± 5.4 mV potential, 84.7 ± 21 μg/mg ALN/total lipids, TL). The effect of nanoARCChol(ALN) was further assessed on severely inflamed HUVECs. To that aim, HUVECs were grown on a porous barrier on top of abasal compartment seeded either with macrophages or human foam cells. One lighter and one more pronounced inflammatorycontext was modelled by adding lipopolysaccharide (LPS) to the apical or the apical and basal compartments. The endocytosis ofnanoARC-Chol(ALN), was observed to partly reduce the endothelial-mesenchymal transition of HUVECs. Besides, while10 mg/mL dexamethasone, 7.6 mM free ALN and ALN-loaded liposomes failed, 50 μg/mL TL + 2.5 μg/mL ALN (i.e., nanoARCChol(ALN)) reduced the IL-6 and IL-8 levels by, respectively, 75% and 65% in the mild and by, respectively, 60% and 40% in thepronounced inflammation model. This is the first report showing that the endocytosis of nanoARC-Chol(ALN) by HUVECs magnifiesthe anti-inflammatory activity of ALN even under conditions of intense irritation, not only surpassing that of free ALN but alsothat of dexamethasone.
Fil: Jerez, Horacio Emanuel. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología. Area Química; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Simioni, Yamila Roxana. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología. Area Química; Argentina
Fil: Ghosal, Kajal. Jadavpur University; India
Fil: Morilla, María José. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología. Area Química; Argentina
Fil: Romero, Eder Lilia. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología. Area Química; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Materia
alendronate
archaeosomes
endothelial
inflammation
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/238557
Acceder
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network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Cholesterol nanoarchaeosomes for alendronate targeted delivery as an anti-endothelial dysfunction agentJerez, Horacio EmanuelSimioni, Yamila RoxanaGhosal, KajalMorilla, María JoséRomero, Eder Liliaalendronatearchaeosomesendothelialinflammationhttps://purl.org/becyt/ford/2.9https://purl.org/becyt/ford/2Sodium alendronate (ALN) is a very hydrosoluble and poorly permeable molecule used as an antiresorptive agent and with vascularanticalcifying capacity. Loaded into targeted nanovesicles, its anti-inflammatory activity may be amplified towards extra-osseousand noncalcified target cells, such as severely irritated vascular endothelium. Here cytotoxicity, mitochondrial membrane potential,ATP content, and membrane fluidity of human endothelial venous cells (HUVECs) were determined after endocytosis of ALNloadednanoarchaeosomes (nanoARC-Chol(ALN), made of polar lipids from Halorubrum tebenquichense: cholesterol 7:3 w/w,166 ± 5 nm, 0.16 ± 0.02 PDI, −40.8 ± 5.4 mV potential, 84.7 ± 21 μg/mg ALN/total lipids, TL). The effect of nanoARCChol(ALN) was further assessed on severely inflamed HUVECs. To that aim, HUVECs were grown on a porous barrier on top of abasal compartment seeded either with macrophages or human foam cells. One lighter and one more pronounced inflammatorycontext was modelled by adding lipopolysaccharide (LPS) to the apical or the apical and basal compartments. The endocytosis ofnanoARC-Chol(ALN), was observed to partly reduce the endothelial-mesenchymal transition of HUVECs. Besides, while10 mg/mL dexamethasone, 7.6 mM free ALN and ALN-loaded liposomes failed, 50 μg/mL TL + 2.5 μg/mL ALN (i.e., nanoARCChol(ALN)) reduced the IL-6 and IL-8 levels by, respectively, 75% and 65% in the mild and by, respectively, 60% and 40% in thepronounced inflammation model. This is the first report showing that the endocytosis of nanoARC-Chol(ALN) by HUVECs magnifiesthe anti-inflammatory activity of ALN even under conditions of intense irritation, not only surpassing that of free ALN but alsothat of dexamethasone.Fil: Jerez, Horacio Emanuel. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología. Area Química; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Simioni, Yamila Roxana. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología. Area Química; ArgentinaFil: Ghosal, Kajal. Jadavpur University; IndiaFil: Morilla, María José. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología. Area Química; ArgentinaFil: Romero, Eder Lilia. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología. Area Química; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaBeilstein-Institut2024-05info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/238557Jerez, Horacio Emanuel; Simioni, Yamila Roxana; Ghosal, Kajal; Morilla, María José; Romero, Eder Lilia; Cholesterol nanoarchaeosomes for alendronate targeted delivery as an anti-endothelial dysfunction agent; Beilstein-Institut; Beilstein Journal of Nanotechnology; 15; 5-2024; 517-5342190-4286CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://www.beilstein-journals.org/bjnano/articles/15/46info:eu-repo/semantics/altIdentifier/doi/10.3762/bjnano.15.46info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-10T13:12:27Zoai:ri.conicet.gov.ar:11336/238557instacron: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 13:12:28.026CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Cholesterol nanoarchaeosomes for alendronate targeted delivery as an anti-endothelial dysfunction agent
title Cholesterol nanoarchaeosomes for alendronate targeted delivery as an anti-endothelial dysfunction agent
spellingShingle Cholesterol nanoarchaeosomes for alendronate targeted delivery as an anti-endothelial dysfunction agent
Jerez, Horacio Emanuel
alendronate
archaeosomes
endothelial
inflammation
title_short Cholesterol nanoarchaeosomes for alendronate targeted delivery as an anti-endothelial dysfunction agent
title_full Cholesterol nanoarchaeosomes for alendronate targeted delivery as an anti-endothelial dysfunction agent
title_fullStr Cholesterol nanoarchaeosomes for alendronate targeted delivery as an anti-endothelial dysfunction agent
title_full_unstemmed Cholesterol nanoarchaeosomes for alendronate targeted delivery as an anti-endothelial dysfunction agent
title_sort Cholesterol nanoarchaeosomes for alendronate targeted delivery as an anti-endothelial dysfunction agent
dc.creator.none.fl_str_mv Jerez, Horacio Emanuel
Simioni, Yamila Roxana
Ghosal, Kajal
Morilla, María José
Romero, Eder Lilia
author Jerez, Horacio Emanuel
author_facet Jerez, Horacio Emanuel
Simioni, Yamila Roxana
Ghosal, Kajal
Morilla, María José
Romero, Eder Lilia
author_role author
author2 Simioni, Yamila Roxana
Ghosal, Kajal
Morilla, María José
Romero, Eder Lilia
author2_role author
author
author
author
dc.subject.none.fl_str_mv alendronate
archaeosomes
endothelial
inflammation
topic alendronate
archaeosomes
endothelial
inflammation
purl_subject.fl_str_mv https://purl.org/becyt/ford/2.9
https://purl.org/becyt/ford/2
dc.description.none.fl_txt_mv Sodium alendronate (ALN) is a very hydrosoluble and poorly permeable molecule used as an antiresorptive agent and with vascularanticalcifying capacity. Loaded into targeted nanovesicles, its anti-inflammatory activity may be amplified towards extra-osseousand noncalcified target cells, such as severely irritated vascular endothelium. Here cytotoxicity, mitochondrial membrane potential,ATP content, and membrane fluidity of human endothelial venous cells (HUVECs) were determined after endocytosis of ALNloadednanoarchaeosomes (nanoARC-Chol(ALN), made of polar lipids from Halorubrum tebenquichense: cholesterol 7:3 w/w,166 ± 5 nm, 0.16 ± 0.02 PDI, −40.8 ± 5.4 mV potential, 84.7 ± 21 μg/mg ALN/total lipids, TL). The effect of nanoARCChol(ALN) was further assessed on severely inflamed HUVECs. To that aim, HUVECs were grown on a porous barrier on top of abasal compartment seeded either with macrophages or human foam cells. One lighter and one more pronounced inflammatorycontext was modelled by adding lipopolysaccharide (LPS) to the apical or the apical and basal compartments. The endocytosis ofnanoARC-Chol(ALN), was observed to partly reduce the endothelial-mesenchymal transition of HUVECs. Besides, while10 mg/mL dexamethasone, 7.6 mM free ALN and ALN-loaded liposomes failed, 50 μg/mL TL + 2.5 μg/mL ALN (i.e., nanoARCChol(ALN)) reduced the IL-6 and IL-8 levels by, respectively, 75% and 65% in the mild and by, respectively, 60% and 40% in thepronounced inflammation model. This is the first report showing that the endocytosis of nanoARC-Chol(ALN) by HUVECs magnifiesthe anti-inflammatory activity of ALN even under conditions of intense irritation, not only surpassing that of free ALN but alsothat of dexamethasone.
Fil: Jerez, Horacio Emanuel. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología. Area Química; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Simioni, Yamila Roxana. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología. Area Química; Argentina
Fil: Ghosal, Kajal. Jadavpur University; India
Fil: Morilla, María José. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología. Area Química; Argentina
Fil: Romero, Eder Lilia. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología. Area Química; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
description Sodium alendronate (ALN) is a very hydrosoluble and poorly permeable molecule used as an antiresorptive agent and with vascularanticalcifying capacity. Loaded into targeted nanovesicles, its anti-inflammatory activity may be amplified towards extra-osseousand noncalcified target cells, such as severely irritated vascular endothelium. Here cytotoxicity, mitochondrial membrane potential,ATP content, and membrane fluidity of human endothelial venous cells (HUVECs) were determined after endocytosis of ALNloadednanoarchaeosomes (nanoARC-Chol(ALN), made of polar lipids from Halorubrum tebenquichense: cholesterol 7:3 w/w,166 ± 5 nm, 0.16 ± 0.02 PDI, −40.8 ± 5.4 mV potential, 84.7 ± 21 μg/mg ALN/total lipids, TL). The effect of nanoARCChol(ALN) was further assessed on severely inflamed HUVECs. To that aim, HUVECs were grown on a porous barrier on top of abasal compartment seeded either with macrophages or human foam cells. One lighter and one more pronounced inflammatorycontext was modelled by adding lipopolysaccharide (LPS) to the apical or the apical and basal compartments. The endocytosis ofnanoARC-Chol(ALN), was observed to partly reduce the endothelial-mesenchymal transition of HUVECs. Besides, while10 mg/mL dexamethasone, 7.6 mM free ALN and ALN-loaded liposomes failed, 50 μg/mL TL + 2.5 μg/mL ALN (i.e., nanoARCChol(ALN)) reduced the IL-6 and IL-8 levels by, respectively, 75% and 65% in the mild and by, respectively, 60% and 40% in thepronounced inflammation model. This is the first report showing that the endocytosis of nanoARC-Chol(ALN) by HUVECs magnifiesthe anti-inflammatory activity of ALN even under conditions of intense irritation, not only surpassing that of free ALN but alsothat of dexamethasone.
publishDate 2024
dc.date.none.fl_str_mv 2024-05
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/11336/238557
Jerez, Horacio Emanuel; Simioni, Yamila Roxana; Ghosal, Kajal; Morilla, María José; Romero, Eder Lilia; Cholesterol nanoarchaeosomes for alendronate targeted delivery as an anti-endothelial dysfunction agent; Beilstein-Institut; Beilstein Journal of Nanotechnology; 15; 5-2024; 517-534
2190-4286
CONICET Digital
CONICET
url http://hdl.handle.net/11336/238557
identifier_str_mv Jerez, Horacio Emanuel; Simioni, Yamila Roxana; Ghosal, Kajal; Morilla, María José; Romero, Eder Lilia; Cholesterol nanoarchaeosomes for alendronate targeted delivery as an anti-endothelial dysfunction agent; Beilstein-Institut; Beilstein Journal of Nanotechnology; 15; 5-2024; 517-534
2190-4286
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/https://www.beilstein-journals.org/bjnano/articles/15/46
info:eu-repo/semantics/altIdentifier/doi/10.3762/bjnano.15.46
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
application/pdf
dc.publisher.none.fl_str_mv Beilstein-Institut
publisher.none.fl_str_mv Beilstein-Institut
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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