Fast Biofilm Penetration and Anti-PAO1 Activity of Nebulized Azithromycin in Nanoarchaeosomes
| Autor: | Eder Lilia Romero, Paulo Cesar Maffia, Barbara Malheiros, Melina María Belén Martínez, Maria Jose Morilla, María Julia Altube, Leandro R.S. Barbosa |
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| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
FÍSICA MOLECULAR
Pharmaceutical Science Microbial Sensitivity Tests INGENIERÍAS Y TECNOLOGÍAS Azithromycin INHALATION Microbiology ARCHAEOLIPID BILAYER Nanocapsules X-Ray Diffraction Cell Line Tumor Ingeniería de los Materiales Drug Discovery medicine Humans Halorubrum Phospholipids Chemistry ANTIBIOTIC TRAPPING Cryoelectron Microscopy Mucins Biofilm Epithelial Cells Penetration (firestop) Lipids Anti-Bacterial Agents purl.org/becyt/ford/2 [https] A549 Cells Biofilms Liposomes Pseudomonas aeruginosa Molecular Medicine purl.org/becyt/ford/2.5 [https] medicine.drug |
| Zdroj: | CONICET Digital (CONICET) Consejo Nacional de Investigaciones Científicas y Técnicas instacron:CONICET Repositório Institucional da USP (Biblioteca Digital da Produção Intelectual) Universidade de São Paulo (USP) instacron:USP |
| DOI: | 10.1021/acs.molpharmaceut.9b00721 |
| Popis: | 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 |
| Databáze: | OpenAIRE |
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