Fast Biofilm Penetration and Anti-PAO1 Activity of Nebulized Azithromycin in Nanoarchaeosomes

Autores
Altube, María Julia; Martínez, Melina María Belén; Malheiros, Barbara; Maffía, Paulo C.; Barbosa, Leandro R. S.; Morilla, María José; Romero, Eder Lilia
Año de publicación
2020
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Azithromycin (AZ) is a broad-spectrum antibiotic with anti-inflammatory and antiquorum sensing activity against biofilm forming bacteria such as Pseudomonas aeruginosa. AZ administered by oral or parenteral routes, however, neither efficiently accesses nor remains in therapeutic doses inside pulmonary biofilm depths. Instead, inhaled nanocarriers loaded with AZ may revert the problem of low accessibility and permanence of AZ into biofilms, enhancing its antimicrobial activity. The first inhalable nanovesicle formulation of AZ, nanoarchaeosome-AZ (nanoARC-AZ), is here presented. NanoARC prepared with total polar archaeolipids (TPAs), rich in 2,3-di-O-phytanyl-sn-glycero-1-phospho-(3′-sn-glycerol-1′-methylphosphate) (PGP-Me) from Halorubrum tebenquichense archaebacteria, consisted of ∼180 nm-diameter nanovesicles, loaded with 0.28 w/w AZ/TPA. NanoARC-AZ displayed lower minimal inhibitory concentration and minimal bactericidal concentration, higher preformed biofilm disruptive, and anti-PAO1 activity in biofilms than AZ. NanoARC penetrated and disrupted the structure of the PAO1 biofilm within only 1 h. Two milliliters of 15 μg/mL AZ nanoARC-AZ nebulized for 5 min rendered AZ doses compatible with in vitro antibacterial activity. The strong association between AZ and the nanoARC bilayer, combined with electrostatic attraction and trapping into perpendicular methyl groups of archaeolipids, as determined by Laurdan fluorescence anisotropy, generalized polarization, and small-angle X-ray scattering, was critical to stabilize during storage and endure shear forces of nebulization. NanoARC-AZ was noncytotoxic on A549 cells and human THP-1-derived macrophages, deserving further preclinical exploration as enhancers of AZ anti-PAO1 activity.
Fil: Altube, María Julia. Universidad Nacional de Quilmes; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Martínez, Melina María Belén. Universidad Nacional de Quilmes; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Malheiros, Barbara. Universidade de Sao Paulo; Brasil
Fil: Maffía, Paulo C.. Universidad Nacional de Quilmes; Argentina
Fil: Barbosa, Leandro R. S.. Universidade de Sao Paulo; Brasil
Fil: Morilla, María José. Universidad Nacional de Quilmes; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Romero, Eder Lilia. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Quilmes; Argentina
Materia
ANTIBIOTIC TRAPPING
ARCHAEOLIPID BILAYER
INHALATION
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:11336/117998
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/117998
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Fast Biofilm Penetration and Anti-PAO1 Activity of Nebulized Azithromycin in NanoarchaeosomesAltube, María JuliaMartínez, Melina María BelénMalheiros, BarbaraMaffía, Paulo C.Barbosa, Leandro R. S.Morilla, María JoséRomero, Eder LiliaANTIBIOTIC TRAPPINGARCHAEOLIPID BILAYERINHALATIONhttps://purl.org/becyt/ford/2.5https://purl.org/becyt/ford/2Azithromycin (AZ) is a broad-spectrum antibiotic with anti-inflammatory and antiquorum sensing activity against biofilm forming bacteria such as Pseudomonas aeruginosa. AZ administered by oral or parenteral routes, however, neither efficiently accesses nor remains in therapeutic doses inside pulmonary biofilm depths. Instead, inhaled nanocarriers loaded with AZ may revert the problem of low accessibility and permanence of AZ into biofilms, enhancing its antimicrobial activity. The first inhalable nanovesicle formulation of AZ, nanoarchaeosome-AZ (nanoARC-AZ), is here presented. NanoARC prepared with total polar archaeolipids (TPAs), rich in 2,3-di-O-phytanyl-sn-glycero-1-phospho-(3′-sn-glycerol-1′-methylphosphate) (PGP-Me) from Halorubrum tebenquichense archaebacteria, consisted of ∼180 nm-diameter nanovesicles, loaded with 0.28 w/w AZ/TPA. NanoARC-AZ displayed lower minimal inhibitory concentration and minimal bactericidal concentration, higher preformed biofilm disruptive, and anti-PAO1 activity in biofilms than AZ. NanoARC penetrated and disrupted the structure of the PAO1 biofilm within only 1 h. Two milliliters of 15 μg/mL AZ nanoARC-AZ nebulized for 5 min rendered AZ doses compatible with in vitro antibacterial activity. The strong association between AZ and the nanoARC bilayer, combined with electrostatic attraction and trapping into perpendicular methyl groups of archaeolipids, as determined by Laurdan fluorescence anisotropy, generalized polarization, and small-angle X-ray scattering, was critical to stabilize during storage and endure shear forces of nebulization. NanoARC-AZ was noncytotoxic on A549 cells and human THP-1-derived macrophages, deserving further preclinical exploration as enhancers of AZ anti-PAO1 activity.Fil: Altube, María Julia. Universidad Nacional de Quilmes; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Martínez, Melina María Belén. Universidad Nacional de Quilmes; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Malheiros, Barbara. Universidade de Sao Paulo; BrasilFil: Maffía, Paulo C.. Universidad Nacional de Quilmes; ArgentinaFil: Barbosa, Leandro R. S.. Universidade de Sao Paulo; BrasilFil: Morilla, María José. Universidad Nacional de Quilmes; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Romero, Eder Lilia. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Quilmes; ArgentinaAmerican Chemical Society2020-01info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/117998Altube, María Julia; Martínez, Melina María Belén; Malheiros, Barbara; Maffía, Paulo C.; Barbosa, Leandro R. S.; et al.; Fast Biofilm Penetration and Anti-PAO1 Activity of Nebulized Azithromycin in Nanoarchaeosomes; American Chemical Society; Molecular Pharmaceutics; 17; 1; 1-2020; 70-831543-8384CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.1021/acs.molpharmaceut.9b00721info:eu-repo/semantics/altIdentifier/url/https://pubs.acs.org/doi/10.1021/acs.molpharmaceut.9b00721info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2026-03-31T14:56:13Zoai:ri.conicet.gov.ar:11336/117998instacron: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:34982026-03-31 14:56:14.206CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Fast Biofilm Penetration and Anti-PAO1 Activity of Nebulized Azithromycin in Nanoarchaeosomes
title Fast Biofilm Penetration and Anti-PAO1 Activity of Nebulized Azithromycin in Nanoarchaeosomes
spellingShingle Fast Biofilm Penetration and Anti-PAO1 Activity of Nebulized Azithromycin in Nanoarchaeosomes
Altube, María Julia
ANTIBIOTIC TRAPPING
ARCHAEOLIPID BILAYER
INHALATION
title_short Fast Biofilm Penetration and Anti-PAO1 Activity of Nebulized Azithromycin in Nanoarchaeosomes
title_full Fast Biofilm Penetration and Anti-PAO1 Activity of Nebulized Azithromycin in Nanoarchaeosomes
title_fullStr Fast Biofilm Penetration and Anti-PAO1 Activity of Nebulized Azithromycin in Nanoarchaeosomes
title_full_unstemmed Fast Biofilm Penetration and Anti-PAO1 Activity of Nebulized Azithromycin in Nanoarchaeosomes
title_sort Fast Biofilm Penetration and Anti-PAO1 Activity of Nebulized Azithromycin in Nanoarchaeosomes
dc.creator.none.fl_str_mv Altube, María Julia
Martínez, Melina María Belén
Malheiros, Barbara
Maffía, Paulo C.
Barbosa, Leandro R. S.
Morilla, María José
Romero, Eder Lilia
author Altube, María Julia
author_facet Altube, María Julia
Martínez, Melina María Belén
Malheiros, Barbara
Maffía, Paulo C.
Barbosa, Leandro R. S.
Morilla, María José
Romero, Eder Lilia
author_role author
author2 Martínez, Melina María Belén
Malheiros, Barbara
Maffía, Paulo C.
Barbosa, Leandro R. S.
Morilla, María José
Romero, Eder Lilia
author2_role author
author
author
author
author
author
dc.subject.none.fl_str_mv ANTIBIOTIC TRAPPING
ARCHAEOLIPID BILAYER
INHALATION
topic ANTIBIOTIC TRAPPING
ARCHAEOLIPID BILAYER
INHALATION
purl_subject.fl_str_mv https://purl.org/becyt/ford/2.5
https://purl.org/becyt/ford/2
dc.description.none.fl_txt_mv Azithromycin (AZ) is a broad-spectrum antibiotic with anti-inflammatory and antiquorum sensing activity against biofilm forming bacteria such as Pseudomonas aeruginosa. AZ administered by oral or parenteral routes, however, neither efficiently accesses nor remains in therapeutic doses inside pulmonary biofilm depths. Instead, inhaled nanocarriers loaded with AZ may revert the problem of low accessibility and permanence of AZ into biofilms, enhancing its antimicrobial activity. The first inhalable nanovesicle formulation of AZ, nanoarchaeosome-AZ (nanoARC-AZ), is here presented. NanoARC prepared with total polar archaeolipids (TPAs), rich in 2,3-di-O-phytanyl-sn-glycero-1-phospho-(3′-sn-glycerol-1′-methylphosphate) (PGP-Me) from Halorubrum tebenquichense archaebacteria, consisted of ∼180 nm-diameter nanovesicles, loaded with 0.28 w/w AZ/TPA. NanoARC-AZ displayed lower minimal inhibitory concentration and minimal bactericidal concentration, higher preformed biofilm disruptive, and anti-PAO1 activity in biofilms than AZ. NanoARC penetrated and disrupted the structure of the PAO1 biofilm within only 1 h. Two milliliters of 15 μg/mL AZ nanoARC-AZ nebulized for 5 min rendered AZ doses compatible with in vitro antibacterial activity. The strong association between AZ and the nanoARC bilayer, combined with electrostatic attraction and trapping into perpendicular methyl groups of archaeolipids, as determined by Laurdan fluorescence anisotropy, generalized polarization, and small-angle X-ray scattering, was critical to stabilize during storage and endure shear forces of nebulization. NanoARC-AZ was noncytotoxic on A549 cells and human THP-1-derived macrophages, deserving further preclinical exploration as enhancers of AZ anti-PAO1 activity.
Fil: Altube, María Julia. Universidad Nacional de Quilmes; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Martínez, Melina María Belén. Universidad Nacional de Quilmes; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Malheiros, Barbara. Universidade de Sao Paulo; Brasil
Fil: Maffía, Paulo C.. Universidad Nacional de Quilmes; Argentina
Fil: Barbosa, Leandro R. S.. Universidade de Sao Paulo; Brasil
Fil: Morilla, María José. Universidad Nacional de Quilmes; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Romero, Eder Lilia. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Quilmes; Argentina
description Azithromycin (AZ) is a broad-spectrum antibiotic with anti-inflammatory and antiquorum sensing activity against biofilm forming bacteria such as Pseudomonas aeruginosa. AZ administered by oral or parenteral routes, however, neither efficiently accesses nor remains in therapeutic doses inside pulmonary biofilm depths. Instead, inhaled nanocarriers loaded with AZ may revert the problem of low accessibility and permanence of AZ into biofilms, enhancing its antimicrobial activity. The first inhalable nanovesicle formulation of AZ, nanoarchaeosome-AZ (nanoARC-AZ), is here presented. NanoARC prepared with total polar archaeolipids (TPAs), rich in 2,3-di-O-phytanyl-sn-glycero-1-phospho-(3′-sn-glycerol-1′-methylphosphate) (PGP-Me) from Halorubrum tebenquichense archaebacteria, consisted of ∼180 nm-diameter nanovesicles, loaded with 0.28 w/w AZ/TPA. NanoARC-AZ displayed lower minimal inhibitory concentration and minimal bactericidal concentration, higher preformed biofilm disruptive, and anti-PAO1 activity in biofilms than AZ. NanoARC penetrated and disrupted the structure of the PAO1 biofilm within only 1 h. Two milliliters of 15 μg/mL AZ nanoARC-AZ nebulized for 5 min rendered AZ doses compatible with in vitro antibacterial activity. The strong association between AZ and the nanoARC bilayer, combined with electrostatic attraction and trapping into perpendicular methyl groups of archaeolipids, as determined by Laurdan fluorescence anisotropy, generalized polarization, and small-angle X-ray scattering, was critical to stabilize during storage and endure shear forces of nebulization. NanoARC-AZ was noncytotoxic on A549 cells and human THP-1-derived macrophages, deserving further preclinical exploration as enhancers of AZ anti-PAO1 activity.
publishDate 2020
dc.date.none.fl_str_mv 2020-01
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/11336/117998
Altube, María Julia; Martínez, Melina María Belén; Malheiros, Barbara; Maffía, Paulo C.; Barbosa, Leandro R. S.; et al.; Fast Biofilm Penetration and Anti-PAO1 Activity of Nebulized Azithromycin in Nanoarchaeosomes; American Chemical Society; Molecular Pharmaceutics; 17; 1; 1-2020; 70-83
1543-8384
CONICET Digital
CONICET
url http://hdl.handle.net/11336/117998
identifier_str_mv Altube, María Julia; Martínez, Melina María Belén; Malheiros, Barbara; Maffía, Paulo C.; Barbosa, Leandro R. S.; et al.; Fast Biofilm Penetration and Anti-PAO1 Activity of Nebulized Azithromycin in Nanoarchaeosomes; American Chemical Society; Molecular Pharmaceutics; 17; 1; 1-2020; 70-83
1543-8384
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.1021/acs.molpharmaceut.9b00721
info:eu-repo/semantics/altIdentifier/url/https://pubs.acs.org/doi/10.1021/acs.molpharmaceut.9b00721
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 Chemical Society
publisher.none.fl_str_mv American Chemical Society
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 12.822162

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