The identification of novel drug candidates for the treatment of diseases like cancer, infectious diseases, or allergies (especially asthma) assigns new tasks for pharmaceutical technology. With respect to drug delivery several problems occur such as low solubility and hence low bioavailability or restriction to inconvenient routes of administration. Nanotechnological approaches promise to circumvent some of these problems, therefore being well suited for future applications as nanomedicines. Furthermore, efficient and sufficient loading is a critical issue that is approached through mesoporous particles and/or through nonspherical particles both offering larger volumes and surfaces. Special interest is laid on the effect of shape of particulate materials on the body and related physiological mechanisms. The modified response of biological systems on different shapes opens a new dimension to adjust particle system interaction. Finally, the biological response to these systems will determine the fate with respect to their therapeutic value. Therefore, the interaction pattern between nonspherical particulate materials and biological systems as well as the production processes are highlighted.
SummaryPhenotypic variation of microbial populations is a well-known phenomenon and may have significant impact on the success of industrial bioprocesses. Flow cytometry (FC) and the large repertoire of fluorescent dyes bring the high-throughput analysis of multiple parameters in single bacterial cells into reach. In this study, we evaluated a set of different fluorescent dyes for suitability in FC single cell analysis of the biotechnological platform organism Corynebacterium glutamicum. Already simple scattering properties of C. glutamicum cells in the flow cytometer were shown to provide valuable information on the growth activity of analysed cells. Furthermore, we used DAPI staining for a FC-based determination of the DNA content of C. glutamicum cells grown on standard minimal or complex media. Characteristic DNA patterns were observed mirroring the typical uncoupled DNA synthesis in the logarithmic (log) growth phase and are in agreement with a symmetric type of cell division of C. glutamicum. Application of the fluorescent dyes Syto 9, propidium iodide, and DiOC2(3) allowed the identification of subpopulations with reduced viability and membrane potential within early log and stationary phase populations. The presented data highlight the potential of FC-based analyses for online monitoring of C. glutamicum bioprocesses and provide a first reference for future applications and protocols.
Fragrances such as eugenol (4-allyl-2-methoxyphenol) and isoeugenol (2-methoxy-4-propenylphenol), naturally found in reasonable quantities in the essential oils of different spices, are not only common causes of contact dermatitis but also known for their antiproliferative actions. Previously, we found a cell cycle arrest and an arylhydrocarbon receptor (AhR)-mediated activation of cytochromes in immortalized keratinocytes (HaCaT) induced by both compounds. In the present study we investigated whether the cell cycle arrest of eugenol and isoeugenol is mediated by the AhR in HaCaT cells. Analysis of the cell cycle status by fluorescence-activated cell sorting (FACS) revealed an arrest of cells (32-34%) in the G0/G1 phase induced by both compounds. This was found in synchronized HaCaT cells, natural HaCaT, and siRNA AhR transfected HaCaT. The induced G0/G1 arrests were reduced in the presence of the highly selective AhR antagonist 3'-methoxy-4'-nitroflavone (MNF). In summary, these results, together with our previous findings that both compounds induce translocation of the AhR into the nucleus, provide good evidence that the effects of eugenol and isoeugenol in skin and keratinocytes are mediated by the AhR. Furthermore, these data suggest that the known growth suppressive effects of these compounds in some skin cells may be mediated by AhR interactions.
Biological barriers, typically, represented by epithelial tissues are the main hindrance against uncontrolled uptake of a variety of substances. However, the delivery across a biological barrier is a crucial factor in the development of drugs. As the permeability of macromolecular drugs is very limited, new delivery strategies have to be developed and further improved. Thereby, nanoparticle carriers offer an enormous potential for the controlled delivery of active substances into the organism. Besides an intensive study for the reason of risk assessment and toxicology, the possible transport enhancement caused by nanoparticles must be quantified. A powerful tool for these studies is in vitro cell culture models imitating the more complex in vivo situation under controlled conditions. We use polyethylenimine as model enhancer mimicking toxicological effects and altered barrier function in the epithelial in vitro model, Calu-3. Cytotoxicity assays based on different mechanisms and transport properties of a low-permeability marker with and without delivery enhancer are described.
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