Artículo
Cholesterol nanoarchaeosomes for alendronate targeted delivery as an anti-endothelial dysfunction agent
Jerez, Horacio Emanuel
; Simioni, Yamila Roxana
; Ghosal, Kajal; Morilla, María José
; Romero, Eder Lilia
Fecha de publicación:
05/2024
Editorial:
Beilstein-Institut
Revista:
Beilstein Journal of Nanotechnology
ISSN:
2190-4286
Idioma:
Inglés
Tipo de recurso:
Artículo publicado
Clasificación temática:
Resumen
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.
Palabras clave:
alendronate
,
archaeosomes
,
endothelial
,
inflammation
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Colecciones
Articulos(SEDE CENTRAL)
Articulos de SEDE CENTRAL
Articulos de SEDE CENTRAL
Citación
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
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