Efavirenz Repurposing Challenges: A Novel Nanomicelle-Based Antiviral Therapy Against Mosquito-Borne Flaviviruses

Autores
Maldonado, Sofía; Fuentes, Pedro; Bernabeu, Ezequiel Adrian; Bertera, Facundo Martin; Opezzo, Javier; Lagomarsino, Eduardo; Lee, Hyun J.; Martínez Rodríguez, Fleming; Choi, Marcelo Roberto; Salgueiro, María Jimena; Damonte, Elsa Beatriz; Höcht, Christian; Moretton, Marcela Analía; Sepúlveda, Claudia Soledad; Chiappetta, Diego Andrés
Año de publicación
2025
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Background/Objective: World Health Organization latest statistics state that 17%of infectious diseases are transmitted by vectors, causing more than 700,000 deaths eachyear. Particularly, dengue (DENV), Zika (ZIKV) and yellow fever (YFV) viral infectionshave generated international awareness due to their epidemic proportion and risks ofinternational spread. In this framework, the repositioning strategy of Efavirenz (EFV)represents a key clinical feature to improve different antiviral therapies. Therefore, thedevelopment of Soluplus®-based nanomicelles (NMs) loaded with EFV (10 mg/mL) foroptimized oral pharmacotherapy against ZIKV, DENV and YFV infections was investigated.Methods: EFV-NMs were obtained by an acetone diffusion technique. Micellar size andin vitro micellar interaction with mucin were assessed by dynamic light scattering. In vitrocytocompatibility was investigated in A549 and Vero cells and micellar in vitro antiviralactivity against ZIKV, DENV and YFV was evaluated. In vivo oral bioavailability and histologicalstudies were assessed inWistar rats. Results: EFV encapsulation within Soluplus®NMs increased the drug’s apparent aqueous solubility up to 4803-fold with a unimodalmicellar size distribution and a micellar size of ~90 nm at 25 and 37 ◦C. Micellar in vitrointeraction with mucin was also assessed in a pH range of 1.2–7.5 and its storage micellarphysicochemical stability at 4 ◦C was confirmed over 2 years. In vitro cytocompatibilityassays in A549 and Vero cells confirmed that EFV micellar dispersions resulted in safenanoformulations. Interestingly, EFV-loaded NMs exhibited significantly higher in vitroantiviral activity compared with EFV solution for all the tested flaviviruses. In addition the selectivity index (SI) values reveal that EFV-loaded NMs exhibited considerably morebiological efficacy compared to EFV solution in A549 and Vero cell lines and for eachviral infection (SI > 10). Further, the drug pharmacokinetics parameters were enhancedafter the oral administration of EFV-loaded NMs, being biocompatible by not causingdamage in the gastrointestinal segments. Conclusions: Overall, our EFV nanoformulationhighlighted its potential as a novel drug delivery platform for optimized ZIKV, DENV andYFV antiviral therapy.
Fil: Maldonado, Sofía. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Tecnología Farmacéutica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Fuentes, Pedro. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Tecnología Farmacéutica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Bernabeu, Ezequiel Adrian. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Tecnología Farmacéutica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Bertera, Facundo Martin. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Tecnología Farmacéutica; Argentina
Fil: Opezzo, Javier. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Tecnología Farmacéutica; Argentina
Fil: Lagomarsino, Eduardo. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Tecnología Farmacéutica; Argentina
Fil: Lee, Hyun J.. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Martínez Rodríguez, Fleming. Universidad Nacional de Colombia; Colombia
Fil: Choi, Marcelo Roberto. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto Alberto C. Taquini de Investigaciones en Medicina Traslacional - Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Cardiológicas "Prof. Dr. Alberto C. Taquini". Instituto Alberto C. Taquini de Investigaciones en Medicina Traslacional; Argentina
Fil: Salgueiro, María Jimena. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; Argentina
Fil: Damonte, Elsa Beatriz. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; Argentina
Fil: Höcht, Christian. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Farmacología. Cátedra de Farmacología; Argentina
Fil: Moretton, Marcela Analía. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; Argentina
Fil: Sepúlveda, Claudia Soledad. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; Argentina
Fil: Chiappetta, Diego Andrés. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Ciencias Biológicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Materia
EFAVIRENZ
DRUF REPURPOSING
POLIMERIC MICELLES
DENGUE
ZIKA
YELLOW FEVER
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:11336/292072
Acceder
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network_name_str CONICET Digital (CONICET)
spelling Efavirenz Repurposing Challenges: A Novel Nanomicelle-Based Antiviral Therapy Against Mosquito-Borne FlavivirusesMaldonado, SofíaFuentes, PedroBernabeu, Ezequiel AdrianBertera, Facundo MartinOpezzo, JavierLagomarsino, EduardoLee, Hyun J.Martínez Rodríguez, FlemingChoi, Marcelo RobertoSalgueiro, María JimenaDamonte, Elsa BeatrizHöcht, ChristianMoretton, Marcela AnalíaSepúlveda, Claudia SoledadChiappetta, Diego AndrésEFAVIRENZDRUF REPURPOSINGPOLIMERIC MICELLESDENGUEZIKAYELLOW FEVERhttps://purl.org/becyt/ford/3.3https://purl.org/becyt/ford/3Background/Objective: World Health Organization latest statistics state that 17%of infectious diseases are transmitted by vectors, causing more than 700,000 deaths eachyear. Particularly, dengue (DENV), Zika (ZIKV) and yellow fever (YFV) viral infectionshave generated international awareness due to their epidemic proportion and risks ofinternational spread. In this framework, the repositioning strategy of Efavirenz (EFV)represents a key clinical feature to improve different antiviral therapies. Therefore, thedevelopment of Soluplus®-based nanomicelles (NMs) loaded with EFV (10 mg/mL) foroptimized oral pharmacotherapy against ZIKV, DENV and YFV infections was investigated.Methods: EFV-NMs were obtained by an acetone diffusion technique. Micellar size andin vitro micellar interaction with mucin were assessed by dynamic light scattering. In vitrocytocompatibility was investigated in A549 and Vero cells and micellar in vitro antiviralactivity against ZIKV, DENV and YFV was evaluated. In vivo oral bioavailability and histologicalstudies were assessed inWistar rats. Results: EFV encapsulation within Soluplus®NMs increased the drug’s apparent aqueous solubility up to 4803-fold with a unimodalmicellar size distribution and a micellar size of ~90 nm at 25 and 37 ◦C. Micellar in vitrointeraction with mucin was also assessed in a pH range of 1.2–7.5 and its storage micellarphysicochemical stability at 4 ◦C was confirmed over 2 years. In vitro cytocompatibilityassays in A549 and Vero cells confirmed that EFV micellar dispersions resulted in safenanoformulations. Interestingly, EFV-loaded NMs exhibited significantly higher in vitroantiviral activity compared with EFV solution for all the tested flaviviruses. In addition the selectivity index (SI) values reveal that EFV-loaded NMs exhibited considerably morebiological efficacy compared to EFV solution in A549 and Vero cell lines and for eachviral infection (SI > 10). Further, the drug pharmacokinetics parameters were enhancedafter the oral administration of EFV-loaded NMs, being biocompatible by not causingdamage in the gastrointestinal segments. Conclusions: Overall, our EFV nanoformulationhighlighted its potential as a novel drug delivery platform for optimized ZIKV, DENV andYFV antiviral therapy.Fil: Maldonado, Sofía. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Tecnología Farmacéutica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Fuentes, Pedro. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Tecnología Farmacéutica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Bernabeu, Ezequiel Adrian. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Tecnología Farmacéutica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Bertera, Facundo Martin. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Tecnología Farmacéutica; ArgentinaFil: Opezzo, Javier. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Tecnología Farmacéutica; ArgentinaFil: Lagomarsino, Eduardo. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Tecnología Farmacéutica; ArgentinaFil: Lee, Hyun J.. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Martínez Rodríguez, Fleming. Universidad Nacional de Colombia; ColombiaFil: Choi, Marcelo Roberto. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto Alberto C. Taquini de Investigaciones en Medicina Traslacional - Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Cardiológicas "Prof. Dr. Alberto C. Taquini". Instituto Alberto C. Taquini de Investigaciones en Medicina Traslacional; ArgentinaFil: Salgueiro, María Jimena. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; ArgentinaFil: Damonte, Elsa Beatriz. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; ArgentinaFil: Höcht, Christian. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Farmacología. Cátedra de Farmacología; ArgentinaFil: Moretton, Marcela Analía. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; ArgentinaFil: Sepúlveda, Claudia Soledad. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; ArgentinaFil: Chiappetta, Diego Andrés. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Ciencias Biológicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaMDPI2025-02info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/292072Maldonado, Sofía; Fuentes, Pedro; Bernabeu, Ezequiel Adrian; Bertera, Facundo Martin; Opezzo, Javier; et al.; Efavirenz Repurposing Challenges: A Novel Nanomicelle-Based Antiviral Therapy Against Mosquito-Borne Flaviviruses; MDPI; Pharmaceutics; 17; 2; 2-2025; 1-231999-4923CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://www.mdpi.com/1999-4923/17/2/241info:eu-repo/semantics/altIdentifier/doi/10.3390/pharmaceutics17020241info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2026-08-25T15:46:23Zoai:ri.conicet.gov.ar:11336/292072instacron: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:34982026-08-25 15:46:24.166CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Efavirenz Repurposing Challenges: A Novel Nanomicelle-Based Antiviral Therapy Against Mosquito-Borne Flaviviruses
title Efavirenz Repurposing Challenges: A Novel Nanomicelle-Based Antiviral Therapy Against Mosquito-Borne Flaviviruses
spellingShingle Efavirenz Repurposing Challenges: A Novel Nanomicelle-Based Antiviral Therapy Against Mosquito-Borne Flaviviruses
Maldonado, Sofía
EFAVIRENZ
DRUF REPURPOSING
POLIMERIC MICELLES
DENGUE
ZIKA
YELLOW FEVER
title_short Efavirenz Repurposing Challenges: A Novel Nanomicelle-Based Antiviral Therapy Against Mosquito-Borne Flaviviruses
title_full Efavirenz Repurposing Challenges: A Novel Nanomicelle-Based Antiviral Therapy Against Mosquito-Borne Flaviviruses
title_fullStr Efavirenz Repurposing Challenges: A Novel Nanomicelle-Based Antiviral Therapy Against Mosquito-Borne Flaviviruses
title_full_unstemmed Efavirenz Repurposing Challenges: A Novel Nanomicelle-Based Antiviral Therapy Against Mosquito-Borne Flaviviruses
title_sort Efavirenz Repurposing Challenges: A Novel Nanomicelle-Based Antiviral Therapy Against Mosquito-Borne Flaviviruses
dc.creator.none.fl_str_mv Maldonado, Sofía
Fuentes, Pedro
Bernabeu, Ezequiel Adrian
Bertera, Facundo Martin
Opezzo, Javier
Lagomarsino, Eduardo
Lee, Hyun J.
Martínez Rodríguez, Fleming
Choi, Marcelo Roberto
Salgueiro, María Jimena
Damonte, Elsa Beatriz
Höcht, Christian
Moretton, Marcela Analía
Sepúlveda, Claudia Soledad
Chiappetta, Diego Andrés
author Maldonado, Sofía
author_facet Maldonado, Sofía
Fuentes, Pedro
Bernabeu, Ezequiel Adrian
Bertera, Facundo Martin
Opezzo, Javier
Lagomarsino, Eduardo
Lee, Hyun J.
Martínez Rodríguez, Fleming
Choi, Marcelo Roberto
Salgueiro, María Jimena
Damonte, Elsa Beatriz
Höcht, Christian
Moretton, Marcela Analía
Sepúlveda, Claudia Soledad
Chiappetta, Diego Andrés
author_role author
author2 Fuentes, Pedro
Bernabeu, Ezequiel Adrian
Bertera, Facundo Martin
Opezzo, Javier
Lagomarsino, Eduardo
Lee, Hyun J.
Martínez Rodríguez, Fleming
Choi, Marcelo Roberto
Salgueiro, María Jimena
Damonte, Elsa Beatriz
Höcht, Christian
Moretton, Marcela Analía
Sepúlveda, Claudia Soledad
Chiappetta, Diego Andrés
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv EFAVIRENZ
DRUF REPURPOSING
POLIMERIC MICELLES
DENGUE
ZIKA
YELLOW FEVER
topic EFAVIRENZ
DRUF REPURPOSING
POLIMERIC MICELLES
DENGUE
ZIKA
YELLOW FEVER
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.3
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv Background/Objective: World Health Organization latest statistics state that 17%of infectious diseases are transmitted by vectors, causing more than 700,000 deaths eachyear. Particularly, dengue (DENV), Zika (ZIKV) and yellow fever (YFV) viral infectionshave generated international awareness due to their epidemic proportion and risks ofinternational spread. In this framework, the repositioning strategy of Efavirenz (EFV)represents a key clinical feature to improve different antiviral therapies. Therefore, thedevelopment of Soluplus®-based nanomicelles (NMs) loaded with EFV (10 mg/mL) foroptimized oral pharmacotherapy against ZIKV, DENV and YFV infections was investigated.Methods: EFV-NMs were obtained by an acetone diffusion technique. Micellar size andin vitro micellar interaction with mucin were assessed by dynamic light scattering. In vitrocytocompatibility was investigated in A549 and Vero cells and micellar in vitro antiviralactivity against ZIKV, DENV and YFV was evaluated. In vivo oral bioavailability and histologicalstudies were assessed inWistar rats. Results: EFV encapsulation within Soluplus®NMs increased the drug’s apparent aqueous solubility up to 4803-fold with a unimodalmicellar size distribution and a micellar size of ~90 nm at 25 and 37 ◦C. Micellar in vitrointeraction with mucin was also assessed in a pH range of 1.2–7.5 and its storage micellarphysicochemical stability at 4 ◦C was confirmed over 2 years. In vitro cytocompatibilityassays in A549 and Vero cells confirmed that EFV micellar dispersions resulted in safenanoformulations. Interestingly, EFV-loaded NMs exhibited significantly higher in vitroantiviral activity compared with EFV solution for all the tested flaviviruses. In addition the selectivity index (SI) values reveal that EFV-loaded NMs exhibited considerably morebiological efficacy compared to EFV solution in A549 and Vero cell lines and for eachviral infection (SI > 10). Further, the drug pharmacokinetics parameters were enhancedafter the oral administration of EFV-loaded NMs, being biocompatible by not causingdamage in the gastrointestinal segments. Conclusions: Overall, our EFV nanoformulationhighlighted its potential as a novel drug delivery platform for optimized ZIKV, DENV andYFV antiviral therapy.
Fil: Maldonado, Sofía. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Tecnología Farmacéutica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Fuentes, Pedro. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Tecnología Farmacéutica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Bernabeu, Ezequiel Adrian. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Tecnología Farmacéutica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Bertera, Facundo Martin. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Tecnología Farmacéutica; Argentina
Fil: Opezzo, Javier. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Tecnología Farmacéutica; Argentina
Fil: Lagomarsino, Eduardo. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Tecnología Farmacéutica; Argentina
Fil: Lee, Hyun J.. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Martínez Rodríguez, Fleming. Universidad Nacional de Colombia; Colombia
Fil: Choi, Marcelo Roberto. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto Alberto C. Taquini de Investigaciones en Medicina Traslacional - Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Cardiológicas "Prof. Dr. Alberto C. Taquini". Instituto Alberto C. Taquini de Investigaciones en Medicina Traslacional; Argentina
Fil: Salgueiro, María Jimena. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; Argentina
Fil: Damonte, Elsa Beatriz. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; Argentina
Fil: Höcht, Christian. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Farmacología. Cátedra de Farmacología; Argentina
Fil: Moretton, Marcela Analía. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; Argentina
Fil: Sepúlveda, Claudia Soledad. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; Argentina
Fil: Chiappetta, Diego Andrés. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Ciencias Biológicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
description Background/Objective: World Health Organization latest statistics state that 17%of infectious diseases are transmitted by vectors, causing more than 700,000 deaths eachyear. Particularly, dengue (DENV), Zika (ZIKV) and yellow fever (YFV) viral infectionshave generated international awareness due to their epidemic proportion and risks ofinternational spread. In this framework, the repositioning strategy of Efavirenz (EFV)represents a key clinical feature to improve different antiviral therapies. Therefore, thedevelopment of Soluplus®-based nanomicelles (NMs) loaded with EFV (10 mg/mL) foroptimized oral pharmacotherapy against ZIKV, DENV and YFV infections was investigated.Methods: EFV-NMs were obtained by an acetone diffusion technique. Micellar size andin vitro micellar interaction with mucin were assessed by dynamic light scattering. In vitrocytocompatibility was investigated in A549 and Vero cells and micellar in vitro antiviralactivity against ZIKV, DENV and YFV was evaluated. In vivo oral bioavailability and histologicalstudies were assessed inWistar rats. Results: EFV encapsulation within Soluplus®NMs increased the drug’s apparent aqueous solubility up to 4803-fold with a unimodalmicellar size distribution and a micellar size of ~90 nm at 25 and 37 ◦C. Micellar in vitrointeraction with mucin was also assessed in a pH range of 1.2–7.5 and its storage micellarphysicochemical stability at 4 ◦C was confirmed over 2 years. In vitro cytocompatibilityassays in A549 and Vero cells confirmed that EFV micellar dispersions resulted in safenanoformulations. Interestingly, EFV-loaded NMs exhibited significantly higher in vitroantiviral activity compared with EFV solution for all the tested flaviviruses. In addition the selectivity index (SI) values reveal that EFV-loaded NMs exhibited considerably morebiological efficacy compared to EFV solution in A549 and Vero cell lines and for eachviral infection (SI > 10). Further, the drug pharmacokinetics parameters were enhancedafter the oral administration of EFV-loaded NMs, being biocompatible by not causingdamage in the gastrointestinal segments. Conclusions: Overall, our EFV nanoformulationhighlighted its potential as a novel drug delivery platform for optimized ZIKV, DENV andYFV antiviral therapy.
publishDate 2025
dc.date.none.fl_str_mv 2025-02
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/11336/292072
Maldonado, Sofía; Fuentes, Pedro; Bernabeu, Ezequiel Adrian; Bertera, Facundo Martin; Opezzo, Javier; et al.; Efavirenz Repurposing Challenges: A Novel Nanomicelle-Based Antiviral Therapy Against Mosquito-Borne Flaviviruses; MDPI; Pharmaceutics; 17; 2; 2-2025; 1-23
1999-4923
CONICET Digital
CONICET
url http://hdl.handle.net/11336/292072
identifier_str_mv Maldonado, Sofía; Fuentes, Pedro; Bernabeu, Ezequiel Adrian; Bertera, Facundo Martin; Opezzo, Javier; et al.; Efavirenz Repurposing Challenges: A Novel Nanomicelle-Based Antiviral Therapy Against Mosquito-Borne Flaviviruses; MDPI; Pharmaceutics; 17; 2; 2-2025; 1-23
1999-4923
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
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info:eu-repo/semantics/altIdentifier/doi/10.3390/pharmaceutics17020241
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/
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dc.publisher.none.fl_str_mv MDPI
publisher.none.fl_str_mv MDPI
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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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