- Inhalation and Respiratory Drug Delivery
- 3D Printing in Biomedical Research
- Innovative Microfluidic and Catalytic Techniques Innovation
- Microfluidic and Bio-sensing Technologies
- Asthma and respiratory diseases
- Neonatal Respiratory Health Research
- Cell Image Analysis Techniques
- Molecular Communication and Nanonetworks
- Single-cell and spatial transcriptomics
- Cancer Cells and Metastasis
- Extracellular vesicles in disease
- Pneumonia and Respiratory Infections
- Mathematical Biology Tumor Growth
- Respiratory Support and Mechanisms
- Microfluidic and Capillary Electrophoresis Applications
Helmholtz Institute for Pharmaceutical Research Saarland
2019-2024
Saarland University
2019-2024
Boehringer Ingelheim (Germany)
2024
Helmholtz Centre for Infection Research
2021-2023
The evaluation of inhalation toxicity, drug safety and efficacy assessment, as well the investigation complex disease pathomechanisms, are increasingly relying on in vitro lung models. This is due to progressive shift towards human-based systems for more predictive translational research. While several cellular models currently available upper airways, modelling distal alveolar region poses constraints that make standardization reliable relatively difficult. In this work, we present a new...
Abstract In the development of orally inhaled drug products preclinical animal models regularly fail to predict pharmacological as well toxicological responses in humans. Models based on human cells and tissues are potential alternatives experimentation allowing for isolation essential processes biology making them accessible vitro. Here, generation a novel monoclonal cell line “Arlo,” derived from polyclonal alveolar epithelium lentivirus immortalized hAELVi via single‐cell printing, its...
Abstract Bacterial invasion of the respiratory system leads to complex immune responses. In deep alveolar regions, first line defense includes foremost epithelium, surfactant‐rich liquid lining, and macrophages. Typical in vitro models come short mimicking complexity airway environment onset infection; among others, they neither capture relevant anatomical features nor physiological flows innate acinar milieu. Here, novel microfluidic‐based acini‐on‐chips that mimic more closely native...
Microphysiological systems (MPSs) are promising in vitro technologies for physiologically relevant predictions of the human absorption, distribution, metabolism, and excretion (ADME) properties drug candidates. However, polydimethylsiloxane (PDMS), a common material used MPSs, can both adsorb absorb small molecules, thereby compromising experimental results. This study aimed to evaluate feasibility using PDMS-based Emulate gut-on-chip determine first-pass intestinal clearance. In cell-free...
Complex in vitro models, especially those based on human cells and tissues, may successfully reduce or even replace animal models within pre-clinical development of orally inhaled drug products. Microfluidic lung-on-chips are regarded as promising since they allow the culture lung specific cell types under physiological stimuli including perfusion air-liquid interface (ALI) conditions a precisely controlled environment. Currently, though, such not available to broad user community given...
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...
The interplay of particles with pulmonary surfactant, a lipid‐protein material pivotal for lung function, is hypothesized as key factor that has not been routinely considered in the current vitro models when determining fate inhaled nanomaterials. To explain its influence on cellular uptake and protective effects, nanoparticles are studied two alveolar cells, absence or presence surfactant. Composition interfacial performance native human porcine surfactants, commercially available bovine...
Abstract This study describes a complex human in vitro model for evaluating anti‐inflammatory drug response the alveoli that may contribute to reduction of animal testing pre‐clinical stage development. The is based on alveolar epithelial cell line Arlo co‐cultured with macrophages differentiated from THP‐1 line, creating physiological biological microenvironment. To mimic three‐dimensional architecture and dynamic expansion relaxation air‐blood‐barrier, they are grown stretchable...
The pharmaceutical industry is in rising need for alternative methods that minimise animal testing during early drug development, mainly because of the poor transferability from to human, costs or ethical issues. However, traditional cellular models fail reproduce essential physio-pathological, systemic and structural aspects. In this sense, organ-on-chips have emerged as advanced <i>in vitro</i> systems emulating organ microenvironment. Due complex architecture dynamics lungs, a significant...