Publikationen

Dialysis diffusion kinetics are investigated via in situ NMR spectroscopy for numerous different raw polymeric solutions to result in a general guideline for polymer purification using dialysis. In several approaches, a polymer was on purpose contaminated with its respective monomer, regenerated conducting conventional dialysis and monitored online utilizing in situ NMR spectroscopy. Consequently, polymer type and molar mass, monomer type, molar mass cut-off of the dialysis tubing and type of solvent were varied resulting in 29 different purification approaches and over 40 000 NMR-spectra. As a result, several major parameters were identified affecting the purification process significantly such as the chosen solvent, viscosity and alpha value. On the contrary, parameters such as dialysis tubing molar mass cut-off and molar mass of the polymer did not affect the purification in a significant manner. Furthermore, physical properties such as density, viscosity, alpha value, and dipole moment of the ingredients were combined in a principal component analysis in order to identify the most important parameters.

A micro segmented-flow approach was utilized for the isolation soil bacteria that can degrade synthetic polymers as polyethylene glycols (PEG) and polyacrylamide (PAM). We had been able to obtain many strains; among them, five Achromobacter spanius strains from soil samples of specific sampling sites that were connected with ancient human impacts. In addition to the characterization of community responses and isolating single strains, this microfluidic approach allowed for investigation of the susceptibility of Achromobacter spanius strains against three synthetic polymers, including PEG, PAM, and Polyvinylpyrrolidone (PVP) and two organic solvents known as 1,4-dioxane and diglyme. The small stepwise variation of effector concentrations in 500 nL droplets provides a detailed reflection of the concentration-dependent response of bacterial growth and endogenous autofluorescence activity. As a result, all five strains can use PEG600 as carbon source. Furthermore, all strains showed similar dose-response characteristics in 1,4-dioxane and diglyme. However, significantly different PAM- and PVP-tolerances were found for these strains. Samples from the surface soil of prehistorical rampart areas supplied a strain capable of degradation of PEG, PVP, and PAM. This study demonstrates on the one hand, the potential of microsegment flow for miniaturized dose-response screening studies and its ability to detect novel strains, and on the other hand, two of five isolated Achromobacter spanius strains may be useful in providing optimal growth conditions in bioremediation and biodegradation processes.

C60 fullerene (C60) as a nanocarbon particle, compatible with biological structures, capable of penetrating through cell membranes and effectively scavenging free radicals, is widely used in biomedicine. A protective effect of C60 on the biomechanics of fast (m. gastrocnemius) and slow (m. soleus) muscle contraction in rats and the pro- and antioxidant balance of muscle tissue during the development of muscle fatigue was studied compared to the same effect of the known antioxidant N-acetylcysteine (NAC). C60 and NAC were administered intraperitoneally at doses of 1 and 150 mg kg−1, respectively, daily for 5 days and 1 h before the start of the experiment. The following quantitative markers of muscle fatigue were used: the force of muscle contraction, the level of accumulation of secondary products of lipid peroxidation (TBARS) and the oxygen metabolite H2O2, the activity of first-line antioxidant defense enzymes (superoxide dismutase (SOD) and catalase (CAT)), and the condition of the glutathione system (reduced glutathione (GSH) content and the activity of the glutathione peroxidase (GPx) enzyme). The analysis of the muscle contraction force dynamics in rats against the background of induced muscle fatigue showed, that the effect of C60, 1 h after drug administration, was (15-17)% more effective on fast muscles than on slow muscles. A further slight increase in the effect of C60 was revealed after 2 h of drug injection, (7-9)% in the case of m. gastrocnemius and (5-6)% in the case of m. soleus. An increase in the effect of using C60 occurred within 4 days (the difference between 4 and 5 days did not exceed (3-5)%) and exceeded the effect of NAC by (32-34)%. The analysis of biochemical parameters in rat muscle tissues showed that long-term application of C60 contributed to their decrease by (10-30)% and (5-20)% in fast and slow muscles, respectively, on the 5th day of the experiment. At the same time, the protective effect of C60 was higher compared to NAC by (28-44)%. The obtained results indicate the prospect of using C60 as a potential protective nano agent to improve the efficiency of skeletal muscle function by modifying the reactive oxygen species-dependent mechanisms that play an important role in the processes of muscle fatigue development.

The development of precision cancer medicine relies on novel formulation strategies for targeted drug delivery to increase the therapeutic outcome. Biocompatible polymer nanoparticles, namely dextran-graft-polyacrylamide (D-g-PAA) copolymers, represent one of the innovative non-invasive approaches for drug delivery applications in cancer therapy. In this study, the star-like D-g-PAA copolymer in anionic form (D-g-PAAan) was developed for pH-triggered targeted drug delivery of the common chemotherapeutic drugs - doxorubicin (Dox) and cisplatin (Cis). The initial D-g-PAA copolymer was synthesized by the radical graft polymerization method, and then alkaline-hydrolyzed to get this polymer in anionic form for further use for drug encapsulation. The acidification of the buffer promoted the release of loaded drugs. D-g-PAAan nanoparticles increased the toxic potential of the drugs against human and mouse lung carcinoma cells (A549 and LLC), but not against normal human lung cells (HEL299). The drug-loaded D-g-PAAan-nanoparticles promoted further oxidative stress and apoptosis induction in LLC cells. D-g-PAAan-nanoparticles improved Dox accumulation and drugs’ toxicity in a 3D LLC multi-cellular spheroid model. The data obtained indicate that the strategy of chemotherapeutic drug encapsulation within the branched D-g-PAAan nanoparticle allows not only to realize pH-triggered drug release but also to potentiate its cytotoxic, prooxidant and proapoptotic effects against lung carcinoma cells.

A promising strategy to increase the numbers of hematopoietic stem cells (HSCs) for clinical applications, like stem cell transplantation, is offered by advanced in vitro culture systems. We developed artificial 3D bone marrow-like scaffolds made of polydimethylsiloxane (PDMS) mimicking the natural HSC niche in vitro. These 3D PDMS scaffolds in combination with an optimized culture medium allow the amplification of high numbers of undifferentiated HSCs by activating specific molecular signaling pathways.