A5033263762- Inhalation and Respiratory Drug Delivery
- Drug Solubulity and Delivery Systems
- Air Quality and Health Impacts
- Cancer-related Molecular Pathways
- Carcinogens and Genotoxicity Assessment
- Microencapsulation and Drying Processes
- Noise Effects and Management
- Energy and Environment Impacts
- DNA Repair Mechanisms
- Asthma and respiratory diseases
- Nanomaterials for catalytic reactions
- Indoor Air Quality and Microbial Exposure
- Digital Imaging for Blood Diseases
- Toxic Organic Pollutants Impact
- Protein Tyrosine Phosphatases
- Analytical Methods in Pharmaceuticals
- Advanced Drug Delivery Systems
- Nanoparticles: synthesis and applications
- Air Quality Monitoring and Forecasting
- Image Processing and 3D Reconstruction
- Advancements in Transdermal Drug Delivery
- nanoparticles nucleation surface interactions
- Gold and Silver Nanoparticles Synthesis and Applications
- Ubiquitin and proteasome pathways
- Advanced Nanomaterials in Catalysis
Integrated Cardio Metabolic Centre
2024
Karolinska Institutet
2006-2021
Biochemisches Institut für Umweltcarcinogene
2007
Background Exposure to agents via inhalation is of great concerns both in workplace environment and the daily contact with particles ambient air. Reliable human airway exposure systems will most likely replace animal experiment future toxicity assessment studies inhaled agents. Methods In this study, we successfully established a combination an system (XposeALI) 3D models mimicking healthy chronic bronchitis-like mucosa by co-culturing primary bronchial epithelial cells (PBEC) fibroblast at...
Diesel exhaust particles (DEP) are a major component of outdoor air pollution. DEP mediated pulmonary effects plausibly linked to inflammatory and oxidative stress response in which macrophages (MQ), epithelial cells their cell-cell interaction plays crucial role. Therefore, this study we aimed at studying the cellular crosstalk between airway with MQ polarization following exposure aerosolized by assessing inflammation, stress, markers. Lung mucosa models including primary bronchial (PBEC)...
The main purpose of this work was to develop an in vitro method for simulating the dissolution and absorption inhaled dry powder drugs that also mimics systemic pharmacokinetic data. A second evaluate method. DissolvIt® developed as a simulation air-blood barrier upper airways, constituting: "airborne" particles deposited on glass cover slip, mucus simulant, polycarbonate (basal) membrane, pumped albumin buffer pulmonary blood flow. PreciseInhale® exposure system used aerosolize deposit test...
Relevant in vitro assays that can simulate exposure to nanoparticles (NPs) via inhalation are urgently needed. Presently, the most common method employed is expose lung cells under submerged conditions, but cellular responses NPs such conditions might differ from those observed at more physiological air-liquid interface (ALI). The aim of this study was investigate cytotoxic and inflammatory potential CeO2 (NM-212) a co-culture A549 epithelial differentiated THP-1 both ALI conditions....
Mdm2 inactivates the tumor suppressor p53 and Akt has been shown to be a major activator of in many cell types. We have investigated regulation hepatocytes. found that growth factor-induced Ser-166 phosphorylation was inhibited by MEK inhibitors U0126 PD98059 HepG2 cells rat liver line, TRL 1215. Also, bile acids oxidative stress induced at an apparently MEK-ERK-dependent mechanism. In contrast, lung mediated Akt. Further studies revealed phosphatidylinositol 3-kinase LY294002 wortmannin...
The dissolution of inhaled drug particles in the lungs is a challenge to model using biorelevant methods terms (i) collecting respirable emitted aerosol fraction and dose, (ii) presenting this small volume medium that representative lung lining fluid, (iii) measuring low concentrations released. We report developments methodology for each these steps utilize mechanistic silico modeling evaluate vitro profiles context plasma concentration-time profiles. PreciseInhale delivery system was used...
Carbon nanoparticles (CNP) are generated by incomplete combustion of diesel engines. Several epidemiological studies associated higher susceptibility to particulate matter related adverse respiratory outcomes with preexisting conditions like chronic bronchitis (CB). Therefore, we compared the effect CNP exposure on primary bronchial epithelial cells (PBEC) developed in air-liquid interface (ALI) models normal versus CB-like-mucosa.PBEC cultured at ALI represented mucosa (PBEC-ALI). To...
Mdm2 is an oncoprotein interacting with p53 and maintaining low levels in unstressed cells. Here we investigated the effect of genotoxic compounds on phosphorylation levels. Employing 2A10 antibody phosphatase treatment found that accumulated HepG2 cells when exposed to concentrations such as mitomycin C, etoposide, 5-fluorouracil, benzo[a]pyrene (BP). The low-dose responses were not accompanied by accumulation BP was affected small interfering RNA for p53. In human lymphoblasts 10nM induced...
Correlating data from in vitro dissolution testing of inhaled particulate pharmaceuticals or air pollutants with the and distribution to blood circulation same aerosols following inhalation vivo is a major challenge. Better methods could benefit both drug development risk assessment pollutants. Five properties known influence results produced by are particle deposition pattern, barrier thickness, surfactant distribution, perfusion strategy volume dissolution. The purpose this manuscript was...
Background Physiologically relevant cell line-based models of human airway mucosa are needed to assess nanoparticle-mediated pulmonary toxicity for any xenbiotics expsoure study. Palladium nanoparticles (Pd-NP) originating from catalytic converters in vehicles pose health risks. We aimed develop vitro the toxic potential Pd-NP normal (Non-CB) and chronic bronchitis-like (CB-like) models. Methods Bronchial were developed using Epithelial cells (16HBE: apical side) co-cultured with fibroblast...
The human lung cancer cell line A549 was exposed to diol epoxides (DEs) and the effect on DNA damage signaling proteins studied. DEs used were derived from bay-region PAHs chrysene; CDE dibenz[a,h]anthracene; DBADE, or fjord-region benzo[c]chrysene; B[c]CDE, benzo[g]chrysene; B[g]CDE benzo[c]phenanthrene; B[c]PhDE. All induced a rapid response Mdm2, p53 histone H2AX phosphorylation, where Mdm2 most sensitive marker of damage. Fjord-region stronger more persistent studied than DEs. This...