10.1021/acs.molpharmaceut.9b00721.s001
Maria
Julia Altube
Maria
Julia
Altube
Melina M. B. Martínez
Melina M. B.
Martínez
Barbara Malheiros
Barbara
Malheiros
Paulo C. Maffía
Paulo C.
Maffía
Leandro R. S. Barbosa
Leandro R. S.
Barbosa
Maria Jose Morilla
Maria Jose
Morilla
Eder Lilia Romero
Eder Lilia
Romero
Fast Biofilm
Penetration and Anti-PAO1 Activity of
Nebulized Azithromycin in Nanoarchaeosomes
American Chemical Society
2019
biofilm depths
AZ anti-PAO 1 activity
Nebulized Azithromycin
Fast Biofilm Penetration
TPA
THP -1-derived macrophages
nanoARC bilayer
bactericidal concentration
AZ doses
anti-PAO 1 activity
Nanoarchaeosomes Azithromycin
shear forces
inhalable nanovesicle formulation
parenteral routes
inhaled nanocarriers
antimicrobial activity
Anti-PAO 1 Activity
Laurdan fluorescence anisotropy
small-angle X-ray
5 min
methyl groups
549 cells
1 h
PAO 1 biofilm
broad-spectrum antibiotic
Halorubrum tebenquichense archaebacteria
Pseudomonas aeruginosa
glycero -1-phospho sn
preformed biofilm
2019-12-03 15:23:30
Journal contribution
https://acs.figshare.com/articles/journal_contribution/Fast_Biofilm_Penetration_and_Anti-PAO1_Activity_of_Nebulized_Azithromycin_in_Nanoarchaeosomes/11310494
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-<i>O</i>-phytanyl-<i>sn</i>-glycero-1-phospho-(3′-<i>sn</i>-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.