A5048008366- Inhalation and Respiratory Drug Delivery
- Bacterial biofilms and quorum sensing
- Cystic Fibrosis Research Advances
- Antimicrobial Peptides and Activities
- Neonatal Respiratory Health Research
- Pneumonia and Respiratory Infections
- Asthma and respiratory diseases
- Biochemical and Structural Characterization
- Mathematical Biology Tumor Growth
- Antibiotic Resistance in Bacteria
- Biosensors and Analytical Detection
- Cell Image Analysis Techniques
- Microfluidic and Bio-sensing Technologies
- Single-cell and spatial transcriptomics
Saarland University
2020-2021
Helmholtz Institute for Pharmaceutical Research Saarland
2020-2021
Helmholtz Centre for Infection Research
2021
Pseudomonas aeruginosa biofilms cause persistent and chronic infections, most known clinically in cystic fibrosis (CF). Tobramycin (TOB) is a standard anti-pseudomonal antibiotic; however, biofilm its efficacy severely decreases due to limited permeability across the matrix. Herewith, biomimetic, nanostructured, lipid liquid crystal nanoparticle-(LCNP)-formulation discovered significantly enhance of TOB eradicate P. infections. Using an advanced, biologically-relevant co-culture model human...
Abstract Pseudomonas aeruginosa (PA) infections can be notoriously difficult to treat and are often accompanied by the development of antimicrobial resistance (AMR). Quorum sensing inhibitors (QSI) acting on PqsR (MvfR) – a crucial transcriptional regulator serving major functions in PA virulence enhance antibiotic efficacy eventually prevent AMR. An integrated drug discovery campaign including design, medicinal chemistry‐driven hit‐to‐lead optimization in‐depth biological profiling new QSI...
fDrug research for the treatment of lung infections is progressing towards predictive in vitro models high complexity. The multifaceted presence bacteria can re-adapt epithelial arrangement, while immune cells coordinate an inflammatory response against microenvironment. While vivo have been choice testing new anti-infectives context cystic fibrosis, they still do not accurately mimic conditions such diseases humans and outcomes. Complex infected airways based on human (bronchial...
The deposition of pre-metered doses (i.e., defined before and not after exposition) at the air–liquid interface viable pulmonary epithelial cells remains an important but challenging task for developing aerosol medicines. While some devices allow quantification deposited dose or during experiment, e.g., gravimetrically, there is still no generally accepted way to deposit small aerosolized drugs pharmaceutical formulations, nanomedicines. Here, we describe a straightforward custom-made...
Pulmonary infections associated with Pseudomonas aeruginosa can be life-threatening for patients suffering from chronic lung diseases such as cystic fibrosis. In this scenario, the formation of biofilms embedded in a mucus layer limit permeation and activity anti-infectives.Native human pulmonary isolated endotracheal tubes, but source is limited large-scale testing. This study, therefore, aimed to evaluate modified artificial sputum medium (ASMmod) mucus-like viscoelastic properties...
As an alternative to technically demanding and ethically debatable animal models, the use of organotypic disease-relevant human cell culture models may improve throughput, speed, success rate for translation novel anti-infectives into clinic. Besides bacterial killing, host viability barrier function appear as relevant but seldomly measured readouts. Moreover, virulence factors signaling molecules are typically not addressed in current models. Here, we describe a reproducible protocol...
fDrug research for the treatment of lung infections is progressing towards predictive in vitro models high complexity. The multifaceted presence bacteria can re-adapt epithelial arrangement, while immune cells coordinate an inflammatory response against microenvironment. While vivo have been choice testing new anti-infectives context cystic fibrosis, they still do not accurately mimic conditions such diseases humans and outcomes. Complex infected airways based on human (bronchial...
In article number 2004369, Martin Empting and colleagues describe a new generation of dual-loaded nanoparticles enabling efficient eradication Pseudomonas aeruginosa biofilms. The squalene-based nanocarrier facilitates co-delivery novel pathogenspecific Quorum Sensing Inhibitor (QSI) together with the standard-of-care antibiotic tobramycin. QSI itself shows high anti-virulence efficacy, favorable DMPK no overt safety pharmacology. When applied as nanoparticle formulation potentiates biofilm...