Dexamethasone nano-embedded sodium hyaluronate microparticles for treatment of COVID-19 acute respiratory distress syndrome
- Autores
- Laura Bertocchi; Cámara, Candelaria Inés; Laura F. Cantú; Elena Del Favero; Ruggero Bettini
- Año de publicación
- 2021
- Idioma
- inglés
- Tipo de recurso
- documento de conferencia
- Estado
- versión publicada
- Descripción
- Dexamethasone (DX) is a synthetic glucocorticoid employed in a wide range of diseases asimmunosuppressant. Recent studies reported that DX could be administered orally or intravenouslyfor the treatment of acute respiratory distress syndrome in patients with COVID-19 phase-3infection caused by an overreaction of their immune system, reducing 28-day mortality in patientsmechanically ventilated or receiving oxygen [1]. Nevertheless, the long-term systemicadministration of dexamethasone led to severe side effects, highlighting the urgent need of newstrategies for its delivery [2][3]. The aim of this work was to develop a new formulation for inhalationbased on DX-nanoparticles. High molecular weight sodium hyaluronate (HA, 750 kDa) was employedto coat DX nanoparticles to exploit HA targeting to CD44 receptors on pulmonary macrophages andits anti-inflammatory effects[4]. DX-nanoparticles were obtained by anti-solvent precipitation usingwater as anti-solvent dripped into an alcoholic solution of drug. The suspension was spray-dried toobtain a dry powder. Size distribution and morphology of microparticles were investigated by laserdiffraction and scanning electron microscopy. Nanoparticle characteristics and composition wereassessed after powder redispersion in physiological medium by dynamic light scattering and X-rayscattering techniques. Results revealed the release of quite polydisperse nanoparticles (PdI = 0.3-0.4) with size around 290 nm in water and 180 nm in phosphate buffer. SAXS results showednanoparticles with a DX-rich crystalline core stabilized in solution by the presence of a shell of HAchains partially embedded in the core. After particle redispersion in water the aerodynamicbehavior of the obtained suspension was assessed in vitro using a device for aerosol therapyobtaining a Fine Particle Fraction of 87.5 +- 0.7% while the Emitted Fraction was 26.4 +-2.9%. Thelatter figure represents a limit that may be overcome by nebulizing directly the nanosuspension inthe pipe of a ventilator.
Fil: Laura Bertocchi. Università di Parma; Italia. Departamento de Alimentos y Drogas ; Universita Degli Studi Di Parma;
Fil: Cámara, Candelaria Inés. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones en Físico-química de Córdoba. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Instituto de Investigaciones en Físico-química de Córdoba; Argentina
Fil: Laura F. Cantú. Universita Degli Studi Di Milano. Dipartimento Di Beitecnologe Mediche E Medicina Traslazionale.; Italia
Fil: Elena Del Favero. Universita Degli Studi Di Milano. Dipartimento Di Beitecnologe Mediche E Medicina Traslazionale.; Italia
Fil: Ruggero Bettini. Departamento de Alimentos y Drogas ; Universita Degli Studi Di Parma;
20th Advanced Course in Pharmaceutical Technology
Italia
Associazione Docenti e Ricercatori Italiani di Tecnologie e Legislazione Farmaceutiche - Materia
-
SARS
respiratory distress syndrome
Hyaluronic Acid-Dexamethasone Nanoparticles
dinamic light scatering
COVID-19 - Nivel de accesibilidad
- acceso abierto
- Condiciones de uso
- https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
- Repositorio
- Institución
- Consejo Nacional de Investigaciones Científicas y Técnicas
- OAI Identificador
- oai:ri.conicet.gov.ar:11336/154395
Ver los metadatos del registro completo
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Dexamethasone nano-embedded sodium hyaluronate microparticles for treatment of COVID-19 acute respiratory distress syndromeLaura BertocchiCámara, Candelaria InésLaura F. CantúElena Del FaveroRuggero BettiniSARSrespiratory distress syndromeHyaluronic Acid-Dexamethasone Nanoparticlesdinamic light scateringCOVID-19https://purl.org/becyt/ford/1.4https://purl.org/becyt/ford/1Dexamethasone (DX) is a synthetic glucocorticoid employed in a wide range of diseases asimmunosuppressant. Recent studies reported that DX could be administered orally or intravenouslyfor the treatment of acute respiratory distress syndrome in patients with COVID-19 phase-3infection caused by an overreaction of their immune system, reducing 28-day mortality in patientsmechanically ventilated or receiving oxygen [1]. Nevertheless, the long-term systemicadministration of dexamethasone led to severe side effects, highlighting the urgent need of newstrategies for its delivery [2][3]. The aim of this work was to develop a new formulation for inhalationbased on DX-nanoparticles. High molecular weight sodium hyaluronate (HA, 750 kDa) was employedto coat DX nanoparticles to exploit HA targeting to CD44 receptors on pulmonary macrophages andits anti-inflammatory effects[4]. DX-nanoparticles were obtained by anti-solvent precipitation usingwater as anti-solvent dripped into an alcoholic solution of drug. The suspension was spray-dried toobtain a dry powder. Size distribution and morphology of microparticles were investigated by laserdiffraction and scanning electron microscopy. Nanoparticle characteristics and composition wereassessed after powder redispersion in physiological medium by dynamic light scattering and X-rayscattering techniques. Results revealed the release of quite polydisperse nanoparticles (PdI = 0.3-0.4) with size around 290 nm in water and 180 nm in phosphate buffer. SAXS results showednanoparticles with a DX-rich crystalline core stabilized in solution by the presence of a shell of HAchains partially embedded in the core. After particle redispersion in water the aerodynamicbehavior of the obtained suspension was assessed in vitro using a device for aerosol therapyobtaining a Fine Particle Fraction of 87.5 +- 0.7% while the Emitted Fraction was 26.4 +-2.9%. Thelatter figure represents a limit that may be overcome by nebulizing directly the nanosuspension inthe pipe of a ventilator.Fil: Laura Bertocchi. Università di Parma; Italia. Departamento de Alimentos y Drogas ; Universita Degli Studi Di Parma;Fil: Cámara, Candelaria Inés. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones en Físico-química de Córdoba. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Instituto de Investigaciones en Físico-química de Córdoba; ArgentinaFil: Laura F. Cantú. Universita Degli Studi Di Milano. Dipartimento Di Beitecnologe Mediche E Medicina Traslazionale.; ItaliaFil: Elena Del Favero. Universita Degli Studi Di Milano. Dipartimento Di Beitecnologe Mediche E Medicina Traslazionale.; ItaliaFil: Ruggero Bettini. Departamento de Alimentos y Drogas ; Universita Degli Studi Di Parma;20th Advanced Course in Pharmaceutical TechnologyItaliaAssociazione Docenti e Ricercatori Italiani di Tecnologie e Legislazione FarmaceuticheAssociazione Docenti e Ricercatori Italiani di Tecnologie e Legislazione Farmaceutiche2021info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/conferenceObjectWorkshopJournalhttp://purl.org/coar/resource_type/c_5794info:ar-repo/semantics/documentoDeConferenciaapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/154395Dexamethasone nano-embedded sodium hyaluronate microparticles for treatment of COVID-19 acute respiratory distress syndrome; 20th Advanced Course in Pharmaceutical Technology; Italia; 2021; 1-1CONICET DigitalCONICETengNacionalinfo:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T10:01:49Zoai:ri.conicet.gov.ar:11336/154395instacron: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:34982025-09-29 10:01:49.248CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse |
dc.title.none.fl_str_mv |
Dexamethasone nano-embedded sodium hyaluronate microparticles for treatment of COVID-19 acute respiratory distress syndrome |
title |
Dexamethasone nano-embedded sodium hyaluronate microparticles for treatment of COVID-19 acute respiratory distress syndrome |
spellingShingle |
Dexamethasone nano-embedded sodium hyaluronate microparticles for treatment of COVID-19 acute respiratory distress syndrome Laura Bertocchi SARS respiratory distress syndrome Hyaluronic Acid-Dexamethasone Nanoparticles dinamic light scatering COVID-19 |
title_short |
Dexamethasone nano-embedded sodium hyaluronate microparticles for treatment of COVID-19 acute respiratory distress syndrome |
title_full |
Dexamethasone nano-embedded sodium hyaluronate microparticles for treatment of COVID-19 acute respiratory distress syndrome |
title_fullStr |
Dexamethasone nano-embedded sodium hyaluronate microparticles for treatment of COVID-19 acute respiratory distress syndrome |
title_full_unstemmed |
Dexamethasone nano-embedded sodium hyaluronate microparticles for treatment of COVID-19 acute respiratory distress syndrome |
title_sort |
Dexamethasone nano-embedded sodium hyaluronate microparticles for treatment of COVID-19 acute respiratory distress syndrome |
dc.creator.none.fl_str_mv |
Laura Bertocchi Cámara, Candelaria Inés Laura F. Cantú Elena Del Favero Ruggero Bettini |
author |
Laura Bertocchi |
author_facet |
Laura Bertocchi Cámara, Candelaria Inés Laura F. Cantú Elena Del Favero Ruggero Bettini |
author_role |
author |
author2 |
Cámara, Candelaria Inés Laura F. Cantú Elena Del Favero Ruggero Bettini |
author2_role |
author author author author |
dc.subject.none.fl_str_mv |
SARS respiratory distress syndrome Hyaluronic Acid-Dexamethasone Nanoparticles dinamic light scatering COVID-19 |
topic |
SARS respiratory distress syndrome Hyaluronic Acid-Dexamethasone Nanoparticles dinamic light scatering COVID-19 |
purl_subject.fl_str_mv |
https://purl.org/becyt/ford/1.4 https://purl.org/becyt/ford/1 |
dc.description.none.fl_txt_mv |
Dexamethasone (DX) is a synthetic glucocorticoid employed in a wide range of diseases asimmunosuppressant. Recent studies reported that DX could be administered orally or intravenouslyfor the treatment of acute respiratory distress syndrome in patients with COVID-19 phase-3infection caused by an overreaction of their immune system, reducing 28-day mortality in patientsmechanically ventilated or receiving oxygen [1]. Nevertheless, the long-term systemicadministration of dexamethasone led to severe side effects, highlighting the urgent need of newstrategies for its delivery [2][3]. The aim of this work was to develop a new formulation for inhalationbased on DX-nanoparticles. High molecular weight sodium hyaluronate (HA, 750 kDa) was employedto coat DX nanoparticles to exploit HA targeting to CD44 receptors on pulmonary macrophages andits anti-inflammatory effects[4]. DX-nanoparticles were obtained by anti-solvent precipitation usingwater as anti-solvent dripped into an alcoholic solution of drug. The suspension was spray-dried toobtain a dry powder. Size distribution and morphology of microparticles were investigated by laserdiffraction and scanning electron microscopy. Nanoparticle characteristics and composition wereassessed after powder redispersion in physiological medium by dynamic light scattering and X-rayscattering techniques. Results revealed the release of quite polydisperse nanoparticles (PdI = 0.3-0.4) with size around 290 nm in water and 180 nm in phosphate buffer. SAXS results showednanoparticles with a DX-rich crystalline core stabilized in solution by the presence of a shell of HAchains partially embedded in the core. After particle redispersion in water the aerodynamicbehavior of the obtained suspension was assessed in vitro using a device for aerosol therapyobtaining a Fine Particle Fraction of 87.5 +- 0.7% while the Emitted Fraction was 26.4 +-2.9%. Thelatter figure represents a limit that may be overcome by nebulizing directly the nanosuspension inthe pipe of a ventilator. Fil: Laura Bertocchi. Università di Parma; Italia. Departamento de Alimentos y Drogas ; Universita Degli Studi Di Parma; Fil: Cámara, Candelaria Inés. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones en Físico-química de Córdoba. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Instituto de Investigaciones en Físico-química de Córdoba; Argentina Fil: Laura F. Cantú. Universita Degli Studi Di Milano. Dipartimento Di Beitecnologe Mediche E Medicina Traslazionale.; Italia Fil: Elena Del Favero. Universita Degli Studi Di Milano. Dipartimento Di Beitecnologe Mediche E Medicina Traslazionale.; Italia Fil: Ruggero Bettini. Departamento de Alimentos y Drogas ; Universita Degli Studi Di Parma; 20th Advanced Course in Pharmaceutical Technology Italia Associazione Docenti e Ricercatori Italiani di Tecnologie e Legislazione Farmaceutiche |
description |
Dexamethasone (DX) is a synthetic glucocorticoid employed in a wide range of diseases asimmunosuppressant. Recent studies reported that DX could be administered orally or intravenouslyfor the treatment of acute respiratory distress syndrome in patients with COVID-19 phase-3infection caused by an overreaction of their immune system, reducing 28-day mortality in patientsmechanically ventilated or receiving oxygen [1]. Nevertheless, the long-term systemicadministration of dexamethasone led to severe side effects, highlighting the urgent need of newstrategies for its delivery [2][3]. The aim of this work was to develop a new formulation for inhalationbased on DX-nanoparticles. High molecular weight sodium hyaluronate (HA, 750 kDa) was employedto coat DX nanoparticles to exploit HA targeting to CD44 receptors on pulmonary macrophages andits anti-inflammatory effects[4]. DX-nanoparticles were obtained by anti-solvent precipitation usingwater as anti-solvent dripped into an alcoholic solution of drug. The suspension was spray-dried toobtain a dry powder. Size distribution and morphology of microparticles were investigated by laserdiffraction and scanning electron microscopy. Nanoparticle characteristics and composition wereassessed after powder redispersion in physiological medium by dynamic light scattering and X-rayscattering techniques. Results revealed the release of quite polydisperse nanoparticles (PdI = 0.3-0.4) with size around 290 nm in water and 180 nm in phosphate buffer. SAXS results showednanoparticles with a DX-rich crystalline core stabilized in solution by the presence of a shell of HAchains partially embedded in the core. After particle redispersion in water the aerodynamicbehavior of the obtained suspension was assessed in vitro using a device for aerosol therapyobtaining a Fine Particle Fraction of 87.5 +- 0.7% while the Emitted Fraction was 26.4 +-2.9%. Thelatter figure represents a limit that may be overcome by nebulizing directly the nanosuspension inthe pipe of a ventilator. |
publishDate |
2021 |
dc.date.none.fl_str_mv |
2021 |
dc.type.none.fl_str_mv |
info:eu-repo/semantics/publishedVersion info:eu-repo/semantics/conferenceObject Workshop Journal http://purl.org/coar/resource_type/c_5794 info:ar-repo/semantics/documentoDeConferencia |
status_str |
publishedVersion |
format |
conferenceObject |
dc.identifier.none.fl_str_mv |
http://hdl.handle.net/11336/154395 Dexamethasone nano-embedded sodium hyaluronate microparticles for treatment of COVID-19 acute respiratory distress syndrome; 20th Advanced Course in Pharmaceutical Technology; Italia; 2021; 1-1 CONICET Digital CONICET |
url |
http://hdl.handle.net/11336/154395 |
identifier_str_mv |
Dexamethasone nano-embedded sodium hyaluronate microparticles for treatment of COVID-19 acute respiratory distress syndrome; 20th Advanced Course in Pharmaceutical Technology; Italia; 2021; 1-1 CONICET Digital CONICET |
dc.language.none.fl_str_mv |
eng |
language |
eng |
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.coverage.none.fl_str_mv |
Nacional |
dc.publisher.none.fl_str_mv |
Associazione Docenti e Ricercatori Italiani di Tecnologie e Legislazione Farmaceutiche |
publisher.none.fl_str_mv |
Associazione Docenti e Ricercatori Italiani di Tecnologie e Legislazione Farmaceutiche |
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reponame:CONICET Digital (CONICET) instname:Consejo Nacional de Investigaciones Científicas y Técnicas |
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CONICET Digital (CONICET) |
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CONICET Digital (CONICET) |
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Consejo Nacional de Investigaciones Científicas y Técnicas |
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CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas |
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dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar |
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