Feasibility of a surface-coated lung model for the quantification of active agent deposition for preclinical studies

Abstract

Multiple drug resistance (MDR) 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)-2,5diphenyltetrazolium bromide (MTT), 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. In this way the deposition of antimicrobial aerosols on the bronchial surfaces is characterized in preliminary tests without any animal experiments.

Investigation of the deposition behaviour and antibacterial effectivity of allicin aerosols and vapour using a lung model

“…The detailed modelling of the test rig has been previously described (28). The qualitative axial velocity distribution through the bronchi is shown as a spectral heatmap in Fig.…”

“…Lung model. The construction details of the lung model have been previously reported (28). The lung model represents the 2nd to 5th generation (the trachea=0th generation) of average life-size bronchial passages in a human lung (Fig.…”

“…It is desirable to know as much as possible about the behaviour of a test substance before progressing to animal trials and in this regard, in this study, we designed and constructed a test rig that accurately recapitulates the air-flow through the life-size 2nd, 3rd, 4th and 5th bronchi of a human lung in order to help characterize the behaviour of inhaled antibiotics. The detailed construction and aerodynamic characteristics of air-flow in this model have been previously reported (28). Herein, we report that using this model, it is possible to demonstrate the dose-dependent efficacy of gentamicin aerosols, and allicin aerosols and vapour.…”