In vitro evaluation of Pseudomonas aeruginosa chronic lung infection models: Are agar and calcium-alginate beads interchangeable?

Torres, Bruna Gaelzer Silva; Awad, Rana; Marchand, Sandrine; Couet, William; Tewes, Frédéric

doi:10.1016/j.ejpb.2019.08.006

Cited by 13 publications

(11 citation statements)

References 53 publications

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“…Agar and alginate are both polymers derived from seaweeds, but they have different chemical properties ( Torres et al, 2019 ). Agar is a neutrally-charged polysaccharide while alginate is anionic, which means they interact with antibiotics differently.…”

Section: Cystic Fibrosis Lung Diseasementioning

confidence: 99%

To bead or not to bead: A review of Pseudomonas aeruginosa lung infection models for cystic fibrosis

et al. 2023

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Cystic fibrosis (CF) lung disease is characterised by recurring bacterial infections resulting in inflammation, lung damage and ultimately respiratory failure. Pseudomonas aeruginosa is considered one of the most important lung pathogens in those with cystic fibrosis. While multiple cystic fibrosis animal models have been developed, many fail to mirror the cystic fibrosis lung disease of humans, including the colonisation by opportunistic environmental pathogens. Delivering bacteria to the lungs of animals in different forms is a way to model cystic fibrosis bacterial lung infections and disease. This review presents an overview of previous models, and factors to consider when generating a new P. aeruginosa lung infection model. The future development and application of lung infection models that more accurately reflect human cystic fibrosis lung disease has the potential to assist in understanding the pathophysiology of cystic fibrosis lung disease and for developing treatments.

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Section: Cystic Fibrosis Lung Diseasementioning

confidence: 99%

To bead or not to bead: A review of Pseudomonas aeruginosa lung infection models for cystic fibrosis

et al. 2023

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“…LVX possesses a potent activity against PA, which, in contrast to tobramycin, is not affected by the presence of CF patients' sputum [32,46,47]. The MP-376 formulation contains Mg 2+ , which complexes LVX, increasing its apparent solubility, and decreasing its bitterness and P app across the biological barrier.…”

Section: Efficacymentioning

confidence: 99%

“…These biofilms, mainly present in the conductive area of the lungs [57], are aggregates of PA (50-100 µm large) entrapped in a selfproduced matrix of anionic polymers (polysaccharides, proteins, eDNA, …), and surrounded by the patient's thick mucus (also composed of anionic polymer) and polymorphonuclear leukocyte. One of the proposed mechanisms that contribute to the decrease in the susceptibility of PA to inhaled cationic antimicrobials, such as tobramycin, is the binding and sequestration of positively charged antibiotics by these anionic polymers [47,[58][59][60]. The sustained pulmonary concentration of CIP in the presence copper is due to the formation of a positively charged complex (CIP-Cu) 2+ that reduces the CIP Papp and lung-blood absorption rate.…”

Section: Efficacymentioning

confidence: 99%

Control of the Lung Residence Time of Highly Permeable Molecules after Nebulization: Example of the Fluoroquinolones

Brillault

Tewes

2020

Pharmaceutics

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Pulmonary drug delivery is a promising strategy to treat lung infectious disease as it allows for a high local drug concentration and low systemic side effects. This is particularly true for low-permeability drugs, such as tobramycin or colistin, that penetrate the lung at a low rate after systemic administration and greatly benefit from lung administration in terms of the local drug concentration. However, for relatively high-permeable drugs, such as fluoroquinolones (FQs), the rate of absorption is so high that the pulmonary administration has no therapeutic advantage compared to systemic or oral administration. Formulation strategies have thus been developed to decrease the absorption rate and increase FQs’ residence time in the lung after inhalation. In the present review, some of these strategies, which generally consist of either decreasing the lung epithelium permeability or decreasing the release rate of FQs into the epithelial lining fluid after lung deposition, are presented in regards to their clinical aspects.

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“…The aim of this study was, therefore, to evaluate the in-vivo efficacy of CIP-Cu complexloaded particles after pulmonary inhalation in model rats that developed chronic pulmonary infection by instillation of Pseudomonas aeruginosa-loaded agar beads [19,20]. This approach has been shown to model the chronic infection and inflammation that affect cystic fibrosis patients [19,21,22].…”

mentioning

confidence: 99%

“…Biofilms can be highly resistant to antibiotics compared to free swimming planktonic bacteria [31]. For example, about ten-to hundred-times more CIP is necessary to inhibit the growth of bacteria as biofilms compared to planktonic bacteria [20,32,33]. P. aeruginosa-entrapped in agar beads once in the lungs for several days resembles P. aeruginosa from biofilms observed in chronic infections [30,34,35].…”

mentioning

confidence: 99%

In vivo efficacy of a dry powder formulation of ciprofloxacin-copper complex in a chronic lung infection model of bioluminescent Pseudomonas aeruginosa

Tewes

Bahamondez-Canas²,

Moraga-Espinoza³

et al. 2020

European Journal of Pharmaceutics and Biopharmaceutics

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A significant limitation of locally delivered treatments for chronic pulmonary infections is often the short residence time within the airways. Ciprofloxacin (CIP), for example, undergoes rapid absorption from the airway lumen. Previously, we demonstrated that the complexation of CIP with copper (CIP-Cu) reduces its apparent epithelial permeability and pulmonary absorption rate without affecting antimicrobial activity against Pseudomonas aeruginosa grown planktonically or as biofilms. This study aimed to evaluate the in vivo efficacy of CIP-Cu, prepared as a dry powder, in a chronic lung infection model. The powders were prepared by jet milling (CIP-HCl) and by spray drying (CIP-Cu). A bioluminescent strain of P. aeruginosa (PAO1::p16Slux) was used to prepare bacteria-loaded agar beads that were inoculated intratracheally to rats. The dynamics of the infection were monitored using luminometry. The bacteria/beads ratio was optimized to allow the highest luminescence signal and animal survival for 8 days. The efficacy of the treatment was evaluated by luminometry in addition to the endpoint (Day 8) where colony counting was performed after lung harvesting. Luminescent P. aeruginosa entrapped in agar beads were useful to monitor the spatial development of the chronic lung infection in rats. The rats were treated with the dry powders in a nose-only inhalation exposure system (NOIES). CIP-Cu and CIP-HCl powders showed similar aerodynamic properties and comparable CIP lung deposition. However, treatment with CIP-Cu significantly (p<0.01) reduced by 4-log the number of CFU of P. aeruginosa per lung in the chronic infection model, whereas CIP-HCl effect was not different from the untreated control group.

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In vitro evaluation of Pseudomonas aeruginosa chronic lung infection models: Are agar and calcium-alginate beads interchangeable?

Cited by 13 publications

References 53 publications

To bead or not to bead: A review of Pseudomonas aeruginosa lung infection models for cystic fibrosis

To bead or not to bead: A review of Pseudomonas aeruginosa lung infection models for cystic fibrosis

Control of the Lung Residence Time of Highly Permeable Molecules after Nebulization: Example of the Fluoroquinolones

In vivo efficacy of a dry powder formulation of ciprofloxacin-copper complex in a chronic lung infection model of bioluminescent Pseudomonas aeruginosa

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