Feasibility study of a surface-coated lung model to quantify active agent deposition for preclinical studies.
Allicin
Antibacterial agent distribution
Bacteria-agar coating
Generic lung model
In vitro treatment
Particle deposition
Journal
Clinical biomechanics (Bristol, Avon)
ISSN: 1879-1271
Titre abrégé: Clin Biomech (Bristol, Avon)
Pays: England
ID NLM: 8611877
Informations de publication
Date de publication:
06 2020
06 2020
Historique:
received:
12
11
2019
revised:
04
03
2020
accepted:
30
04
2020
pubmed:
19
5
2020
medline:
20
2
2021
entrez:
19
5
2020
Statut:
ppublish
Résumé
Multiple drug resistance of a growing number of bacterial pathogens represents an increasing challenge in conventional curative treatments of infectious diseases. However, the development and testing of new antibiotics is associated with a high number of animal experiments. A symmetrical parametrized lung test rig allowing the exposure of air-passage surfaces to antibiotics was designed and tested to demonstrate proof-of-principle with aerosols containing allicin, which is an antimicrobial natural product from garlic. An artificial lung surface is coated with bacteria embedded in a hydrogel and growth inhibition is visualized by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, that is reduced from colourless to the dark blue formazan in the presence of metabolically active, living cells. A nebulizer is used to generate the aerosols. The results show that allicin has an antibiotic effect as an aerosol and that the deposition pattern of the active agent occurred mainly around the carinal regions. The model represents an integral system for continuous, spatial detection of aerosol deposition and allows the analysis of bacterial behaviour and the toxicity of the active agent. Thus, the deposition of antimicrobial aerosols on the bronchial surfaces is characterized in preliminary tests without any animal experiments.
Sections du résumé
BACKGROUND
Multiple drug resistance of a growing number of bacterial pathogens represents an increasing challenge in conventional curative treatments of infectious diseases. However, the development and testing of new antibiotics is associated with a high number of animal experiments.
METHODS
A symmetrical parametrized lung test rig allowing the exposure of air-passage surfaces to antibiotics was designed and tested to demonstrate proof-of-principle with aerosols containing allicin, which is an antimicrobial natural product from garlic. An artificial lung surface is coated with bacteria embedded in a hydrogel and growth inhibition is visualized by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, that is reduced from colourless to the dark blue formazan in the presence of metabolically active, living cells. A nebulizer is used to generate the aerosols.
FINDINGS
The results show that allicin has an antibiotic effect as an aerosol and that the deposition pattern of the active agent occurred mainly around the carinal regions.
INTERPRETATION
The model represents an integral system for continuous, spatial detection of aerosol deposition and allows the analysis of bacterial behaviour and the toxicity of the active agent. Thus, the deposition of antimicrobial aerosols on the bronchial surfaces is characterized in preliminary tests without any animal experiments.
Identifiants
pubmed: 32422391
pii: S0268-0033(20)30147-9
doi: 10.1016/j.clinbiomech.2020.105029
pii:
doi:
Substances chimiques
Aerosols
0
Disulfides
0
Sulfinic Acids
0
allicin
3C39BY17Y6
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
105029Informations de copyright
Copyright © 2020 Elsevier Ltd. All rights reserved.