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dc.contributor.author
Altube, María Julia
dc.contributor.author
Martínez, Melina María Belén
dc.contributor.author
Malheiros, Barbara
dc.contributor.author
Maffia, Paulo Cesar
dc.contributor.author
Barbosa, Leandro R. S.
dc.contributor.author
Morilla, María José
dc.contributor.author
Romero, Eder Lilia
dc.date.available
2022-10-26T17:31:24Z
dc.date.issued
2019-10
dc.identifier.citation
Altube, María Julia; Martínez, Melina María Belén; Malheiros, Barbara; Maffia, Paulo Cesar; Barbosa, Leandro R. S.; et al.; Fast biofilm penetration and anti-PAO1 activity of nebulized azythromicin in nanoarchaeosomes; American Chemical Society; Molecular Pharmaceutics; 17; 1; 10-2019; 70-83
dc.identifier.issn
1543-8384
dc.identifier.uri
http://hdl.handle.net/11336/175017
dc.description.abstract
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.
dc.format
application/pdf
dc.language.iso
eng
dc.publisher
American Chemical Society
dc.rights
info:eu-repo/semantics/restrictedAccess
dc.rights.uri
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.subject
ANTIBIOTIC TRAPPING
dc.subject
ARCHAEOLIPID BILAYER
dc.subject
INHALATION
dc.subject.classification
Bioquímica y Biología Molecular
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Ciencias Biológicas
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CIENCIAS NATURALES Y EXACTAS
dc.title
Fast biofilm penetration and anti-PAO1 activity of nebulized azythromicin in nanoarchaeosomes
dc.type
info:eu-repo/semantics/article
dc.type
info:ar-repo/semantics/artículo
dc.type
info:eu-repo/semantics/publishedVersion
dc.date.updated
2022-10-24T17:45:22Z
dc.journal.volume
17
dc.journal.number
1
dc.journal.pagination
70-83
dc.journal.pais
Estados Unidos
dc.journal.ciudad
Washington
dc.description.fil
Fil: Altube, María Julia. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
dc.description.fil
Fil: Martínez, Melina María Belén. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología. Instituto de Microbiología Básica y Aplicada; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
dc.description.fil
Fil: Malheiros, Barbara. Universidade de Sao Paulo; Brasil
dc.description.fil
Fil: Maffia, Paulo Cesar. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología. Instituto de Microbiología Básica y Aplicada; Argentina
dc.description.fil
Fil: Barbosa, Leandro R. S.. Universidade de Sao Paulo; Brasil
dc.description.fil
Fil: Morilla, María José. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
dc.description.fil
Fil: Romero, Eder Lilia. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
dc.journal.title
Molecular Pharmaceutics
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/url/https://pubs.acs.org/doi/10.1021/acs.molpharmaceut.9b00721
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/doi/http://dx.doi.org/10.1021/acs.molpharmaceut.9b00721
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