A5033750684- RNA Interference and Gene Delivery
- Advanced Drug Delivery Systems
- Advanced biosensing and bioanalysis techniques
- Inhalation and Respiratory Drug Delivery
- Nanoparticle-Based Drug Delivery
- Drug Solubulity and Delivery Systems
- Antimicrobial Peptides and Activities
- Antibiotic Resistance in Bacteria
- Dermatology and Skin Diseases
- Virus-based gene therapy research
- Bacterial biofilms and quorum sensing
- Pneumonia and Respiratory Infections
- Lipid Membrane Structure and Behavior
- Immunotherapy and Immune Responses
- Hair Growth and Disorders
- Neonatal Respiratory Health Research
- Cystic Fibrosis Research Advances
- Advancements in Transdermal Drug Delivery
- Polymer Surface Interaction Studies
- CRISPR and Genetic Engineering
- Hydrogels: synthesis, properties, applications
- Bacteriophages and microbial interactions
- Extracellular vesicles in disease
- Proteins in Food Systems
- Drug Transport and Resistance Mechanisms
Helmholtz Institute for Pharmaceutical Research Saarland
2015-2024
Helmholtz Centre for Infection Research
2015-2024
Saarland University
2014-2024
Leibniz-Institute for New Materials
2018
KIST Europe
2018
Klinikum Saarbrücken
2015-2016
Universität Innsbruck
2006-2008
Gene therapy has always been a promising therapeutic approach for Cystic Fibrosis (CF). However, numerous trials using DNA or viral vectors encoding the correct protein resulted in general low efficacy. In last years, chemically modified messenger RNA (cmRNA) proven to be highly potent, pulmonary drug. Consequently, we first explored expression, function and immunogenicity of human (h)CFTR encoded by cmRNAhCFTR vitro ex vivo, quantified expression flow cytometry, determined its YFP based...
Messenger RNA (mRNA) has gained remarkable attention as an alternative to DNA-based therapies in biomedical research. A variety of biodegradable nanoparticles (NPs) been developed including lipid-based and polymer-based systems for mRNA delivery. However, both still lack achieving efficient transfection rate a detailed understanding the transgene expression kinetics. Therefore, quantitative analysis time-dependent translation behavior would provide better mRNA's transient nature further aid...
Bacterial invasion into eukaryotic cells and the establishment of intracellular infection has proven to be an effective means resisting antibiotic action, as anti-infective agents commonly exhibit a poor permeability across host cell membrane. Encapsulation anti-infectives nanoscaled delivery systems, such liposomes, is shown result in enhancement delivery. The aim current work is, therefore, formulate colistin, poorly permeable anti-infective, liposomes suitable for oral delivery,...
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...
Treatment of microbial infections is becoming daunting because widespread antimicrobial resistance. The treatment challenge further exacerbated by the fact that certain infectious bacteria invade and localize within host cells, protecting from treatments host's immune response. To survive in intracellular niche, such deploy surface receptors similar to cell sequester iron, an essential nutrient for their virulence, iron-binding proteins, particular lactoferrin transferrin. In this context,...
Regarding safety concerns, nonviral gene delivery vehicles that have the required efficiency and for use in human therapy are being widely investigated. The aim of this study was to synthesize evaluate a thiolated chitosan improve efficacy oral systems. Thiolated synthesized by introducing thioglycolic acid (TGA) via amide bond formation mediated carbodiimide. Based on conjugate, nanoparticles with pDNA were generated at pH 4.0 5.0. Cytotoxicity chitosan/pDNA Caco-2 cells evaluated. diameter...
Starch and starch derivatives are widely utilized pharmaceutical excipients. The concept of this study was to make use as a biodegradable backbone modify it with low-toxic, but poor transfecting low molecular weight polyethylenimine (PEI) in order achieve better transfection efficacy while maintaining enzymatic degradability. A sufficiently controllable conjugation could be achieved via water-soluble intermediate oxidized an optimized reaction protocol. Systematic variation MW fraction the...
A miRNA181a/NFAT5 signaling axis promotes immune activation and interferes with the induction of regulatory T cells in islet autoimmunity.
Significance The onset of type 1 diabetes autoimmunity is indicated by the development multiple islet autoantibodies, produced B cells with help T follicular helper (TFH) cells. MicroRNAs (miRNAs) are small noncoding RNAs that regulate cellular states, as immune activation, making them suitable targets for disease intervention. Here, we show an enrichment insulin-specific C-X-C chemokine receptor 5 (CXCR5) + CD4 TFH precursors correlating high miRNA92a abundance during and identify...
Mucus is a complex hydrogel that acts as protective barrier in various parts of the human body. Both composition and structural properties play crucial role maintaining while dictating diffusion molecules (nano)materials. In this study, we compare previously described mucus surrogates with native airway pig intestinal mucus. Oscillatory shear rheology was applied to characterize on bulk macrorheological level, revealing artificial surrogate deviates from elastic-dominant behavior samples. We...
Biodegradable polymeric nanoparticles (NP) made from poly (lactid-co-glycolide) acid (PLGA) and chitosan (CS) hold promise as innovative formulations for targeted delivery. Since interactions of such NP with primary human immune cells have not been characterized, yet, here we assessed the effect PLGA or CS-PLGA treatment on peripheral blood mononuclear (PBMC), well monocyte-derived DC (moDC). Amongst PBMC, antigen presenting (APC) showed higher uptake both preparations than lymphocytes....
Abstract Elimination of pulmonary Pseudomonas aeruginosa (PA) infections is challenging to accomplish with antibiotic therapies, mainly due resistance mechanisms. Quorum sensing inhibitors (QSIs) interfering biofilm formation can thus complement antibiotics. For simultaneous and improved delivery both active agents the infection sites, self‐assembling nanoparticles a newly synthesized squalenyl hydrogen sulfate (SqNPs) were prepared. These nanocarriers allowed for remarkably high loading...
Antimicrobial resistance is becoming more prominent day after due to a number of mechanisms by microbes, especially the sophisticated biological barriers bacteria, in Gram-negatives. There, lipopolysaccharides (LPS) layer unique component outer leaflet membrane which highly impermeable and prevents antibiotics from passing passively into intracellular compartments. Biodynamers, novel class dynamically bio-responsive polymers, may open new perspectives overcome this particular barrier...
Abstract A hydrophobic starch derivative is used for safe and enhanced delivery of anticancer agents. The synthesis characterization propyl with a controlled degree substitution to modulate the release encapsulated drug reported. application this polymer formulating nanoparticles docetaxel, an anti‐cancer agent effective against numerous types cancers but possessing intrinsic formulation difficulties described. solvent emulsification/diffusion technique optimized respect several parameters....
Abstract Pulmonary delivery of nanocarriers for novel antimycobacterial compounds is challenging because the aerodynamic properties nanomaterials are sub-optimal such purposes. Here, we report development dry powder formulations containing benzothiazinone 043 (BTZ) or levofloxacin (LVX), respectively. The intricacy to generate aerosols with adequate while maintaining both nanostructural integrity and compound activity until reaching deeper lung compartments. Microparticles (MPs) were...
Nontuberculous mycobacterial infections rapidly emerge and demand potent medications to cope with resistance. In this context, targeted loco-regional delivery of aerosol medicines the lungs is an advantage. However, sufficient antibiotic requires engineered aerosols for optimized deposition. Here, effect bedaquiline-encapsulating fucosylated versus nonfucosylated liposomes on cellular uptake investigated. Notably, comparison includes critical parameters pulmonary delivery, i.e., deposition...