Projects in Drug Delivery and 3R-Models
INNOVATIVE DRUG DELIVERY SYSTEMS
To convert potent drugs into effective medicines requires suitable carrier systems enabling administration to the human body and absorption across diverse biological barriers. Further, the desired biodistribution ideally directly targeted to the site of action, while protecting the drug against harsh endogenous conditions like pH and metabolic degradation has to be achieved.
We develop different forms of drug carriers, ranging from semi-solid dosage forms, such as ointments and gels, up to solid systems, such as tableted chewing gums, fibers and particles. Besides established techniques for the fabrication of carriers, we apply innovative technologies like electrospinning and microfluidics as novel approaches for designing tailor-made carriers. Electrospinning uses high voltage to generate ultrafine drug-loaded polymer fibers, while the use of microfluidic chips allows for accurate fabrication of droplet- or particle-based systems for drug encapsulation. These techniques show high potential for the incorporation of different drugs including small molecules, fragile biomacromolecules and cells. We currently focus on systems for local delivery to skin and mucosa to combat inflammation as well as infections.
CELL- AND TISSUE-BASED 3R-MODELS
For fundamental understanding of pathophysiological mechanisms as well as absorption and transport processes of drug molecules in the human body, human-relevant models are indispensable. Such models are required for predictive testing of novel medicines. For many diseased states, animal models do not adequately mimic human pathophysiology, thus leading to high attrition rates in preclinical development.
Our research is focused on in vitro models based on human cells and tissues balancing the required level of biological complexity and the applicability for valid and predictive testing. To address the individual scientific demands, our models range from cell monolayers up to complex three-dimensional organotypic cultures integrating multiple human cell types as well as ex vivo tissue biopsies. Besides the use of established hydrogels, we develop bio-inspired, functional materials to simulate the human extracellular matrix for cultivating cells. The models mimic healthy, physiological states, but also disease-relevant conditions, such as inflammation and infection as well as defects like wounds. Their application ranges from basic research and investigation of material-cell interactions up to testing of novel medicines in a (patho)physiologically relevant environment. Particular emphasis is put on the analysis of therapeutic effectiveness, cytotoxicity and cellular uptake to accelerate the translation of these models into clinical application.
Advanced therapeutic concepts require molecular understanding of the interaction between the drug and its carrier system as well as their absorption into tissue and interactions with cells. Established imaging techniques are often destructive or require labelling with bulky marker molecules prone to change the physicochemical properties of the drug and thus falsify the results.
To obtain an in-depth understanding of our drug-loaded carriers and their interaction with biological systems, our analytical spectrum includes established biochemical assays and biophysical tests as well as advanced, label-free techniques like confocal Raman microscopy for non-invasive and chemically-selective characterization. Confocal Raman microscopy is a laser-based, high resolution imaging technique enabling label-free visualization of drug carrier systems and their interaction with cells and biological tissues. Acquisition of spatially resolved Raman spectra allows for discrimination of chemically different components resembling individual “molecular fingerprints” for chemical as well as biological substances. Our applications range from analysis of drug distribution within the carrier and visualization of in situ drug release up to monitoring cell differentiation within our cell- and tissue-based in vitro models and the intracellular fate of our drug carriers.