Publikationen

We designed liposomes dually functionalized with ApoE-derived peptide (mApoE) and chlorotoxin (ClTx) to improve their blood–brain barrier (BBB) crossing. Our results demonstrated the synergistic activity of ClTx-mApoE in boosting doxorubicin-loaded liposomes across the BBB, keeping the anti-tumour activity of the drug loaded: mApoE acts promoting cellular uptake, while ClTx promotes exocytosis of liposomes.

The particular feature of this study is the investigation of effects of pure fluoride- or stannous ions based mouthrinses on the erosion protective properties and the ultrastructure of the in situ pellicle (12 volunteers). Experimental solutions were prepared either from 500 ppm NaF, SMFP, AmF or SnF2 or 1563 ppm SnCl2, respectively. After 1 min of in situ pellicle formation on bovine enamel slabs, rinses with one of the preparations were performed for 1 min and intraoral specimens’ exposure was continued for 28 min. Native enamel slabs and rinses with bidestilled water served as controls. After oral exposure, slabs were incubated in HCl (pH 2; 2.3; 3) for 120 s and kinetics of calcium- and phosphate release were measured photometrically; representative samples were analysed by TEM and EDX. All mouthrinses reduced mineral loss compared to the native 30-min pellicle. The effect was pH-dependent and significant at all pH values only for the tin-containing mouthrinses. No significant differences were observed between the SnF2- and the SnCl2-containing solutions. TEM/EDX confirmed ultrastructural pellicle modifications. SnF2 appears to be the most effective type of fluoride to prevent erosive enamel demineralisation. The observed effects primarily have to be attributed to the stannous ions’ content.

Abstract Bacterial invasion into eukaryotic cells and the establishment of intracellular infection has proven to be an effective means of resisting antibiotic action, as anti-infective agents commonly exhibit a poor permeability across the host cell membrane. Encapsulation of anti-infectives into nanoscaled delivery systems, such as liposomes, is shown to result in an enhancement of intracellular delivery. The aim of the current work is, therefore, to formulate colistin, a poorly permeable anti-infective, into liposomes suitable for oral delivery, and to functionalize these carriers with a bacteria-derived invasive moiety to enhance their intracellular delivery. Different combinations of phospholipids and cholesterol are explored to optimize liposomal drug encapsulation and stability in biorelevant media. These liposomes are then surface-functionalized with extracellular adherence protein (Eap), derived from Staphylococcus aureus. Treatment of HEp-2 and Caco-2 cells infected with Salmonella enterica using colistin-containing, Eap-functionalized liposomes resulted in a significant reduction of intracellular bacteria, in comparison to treatment with nonfunctionalized liposomes as well as colistin alone. This indicates that such bio-invasive carriers are able to facilitate intracellular delivery of colistin, as necessary for intracellular anti-infective activity. The developed Eap-functionalized liposomes, therefore, present a promising strategy for improving the therapy of intracellular infections.

Microbial adhesion and the subsequent formation of resilient biofilms at surfaces are decisively influenced by substrate properties, such as the topography. To date, studies that quantitatively link surface topography and bacterial adhesion are scarce, as both are not straightforward to quantify. To fill this gap, surface morphometry combined with single-cell force spectroscopy was performed on surfaces with irregular topographies on the nano-scale. As surfaces, hydrophobized silicon wafers were used that were etched to exhibit surface structures in the same size range as the bacterial cell wall molecules. The surface structures were characterized by a detailed morphometric analysis based on Minkowski functionals revealing both qualitatively similar features and quantitatively different extensions. We find that as the size of the nanostructures increases, the adhesion forces decrease in a way that can be quantified by the area of the surface that is available for the tethering of cell wall molecules. In addition, we observe a bactericidal effect, which is more pronounced on substrates with taller structures but does not influence adhesion. Our results can be used for a targeted development of 3D-structured materials for/against bio-adhesion. Moreover, the morphometric analysis can serve as a future gold standard for characterizing a broad spectrum of material structures.

Nanoparticulate systems intended for the use in drug delivery are getting more and more complex. Composite nanoparticles, such as core-shell particles are designed in order to be used for co-delivery of drugs or a modified release profile. Often the structure can only be postulated by the preparation process, such as surface polymerization, but cannot be experimentally determined due to a lack of appropriate analytical methods. Here a core-shell particle system composed of two biodegradable and biocompatible materials, gelatin and PLGA, is developed. In order to reveal the actual polymer distribution, a combination of cryo-transmission electron microscopy and energy-filtered transmission electron microscopy was established. Using the occurrence of specific elements in combination with degradation kinetics induced by the electron beam allows to conclude on the nanoparticles’ architecture. Based on these methods and thus, the particle composition, the drug delivery system can be further developed.

The fibrotic encapsulation, which is mainly accompanied by an excessive proliferation of fibroblasts, is an undesired phenomenon after the implantation of various medical devices. Beside the surface chemistry, the topography plays also a major role in the fibroblast-surface interaction. In the present study, one-dimensional aluminium oxide (1D Al2O3) nanostructures with different distribution densities were prepared to reveal the response of human fibroblasts to the surface topography. The cell size, the cell number and the ability to form well-defined actin fibres and focal adhesions were significantly impaired with increasing distribution density of the 1D Al2O3 nanostructures on the substratum.

We propose a theory based on non-equilibrium thermodynamics to describe the mechanical behavior of an active polymer gel created by the inclusion of molecular motors in its solvent. When activated, these motors attach to the chains of the polymer network and shorten them creating a global contraction of the gel, which mimics the active behavior of a cytoskeleton. The power generated by these motors is obtained by an ATP hydrolysis reaction, which transduces chemical energy into mechanical work. The latter is described by an increment of strain energy in the gel due to an increased stiffness. This effect is described with an increment of the cross-link density in the polymer network, which reduces its entropy. The theory then considers polymer network swelling and species diffusion to describe the transient passive behavior of the gel. We finally formulate the problem of uniaxial contraction of a slab of gel and compare the results with experiments, showing good agreement.

This paper outlines an elastoplastic design approach for beam and plate structures subjected to transverse pressure loads and thermal stresses. The purpose of this study is to overcome the limitations of yield-limited designs by exploiting plastic design theorems. The feasible design space of a clamped beam/plate structure subjected to combined thermomechanical loads is explored considering shakedown (stabilized plasticity) as the design criteria. Analytic and numerical solutions are developed that show that allowing shakedown to occur extends the design space and acceptable loading range. In addition, the structures considered here are also prone to buckling due to thermal loads. In this work, interactions between thermal buckling and shakedown are investigated using numerical parametric studies. It is found that buckling enhances elastoplastic shakedown performance which expands the feasible design domain significantly when high aspect ratio beams are considered. In particular it is shown that the enhancement is 2–4 times for the range of aspect ratios examined.

An electro-chemo-mechanical formulation of ion transport in solid electrolytes, in particular for binary systems, is presented. Starting with conservation laws and the second law of thermodynamic, we state a consistent Helmholtz-energy-based framework taking electrostatics, component transport and nonlinear elastic mechanical interaction into account. With the help of finite strain continuum mechanics, we include the effect of geometry changes on ion transport. Changes of local concentration cause swelling and shrinkage and hence stress assisted diffusion. Further coupling originates via an osmotic pressure. Since binary systems are of special interest in battery applications, we formulate both, a fully resolved and an electroneutral model for ion transport. The latter turns out to be an extended version of Newman’s concentrated solution theory taking mechanical effects into account. We demonstrate the importance of these mechanical effects by means of double layers adjacent to blocking electrodes and concentration profiles during galvanostatic charging. Further, we investigate the effect of external deformation as, e.g. found in dendrite growth.

The Butler-Volmer equation is widely used to describe ion-transport across an interface in electrochemical systems. In recent years, a strong focus has been placed on solid state batteries with Li-metal electrodes which promise an increase of energy density and safety, but also introduce new complexity, for example, due to the process of material deposition and stripping which is conceptually different to intercalation and de-intercalation. Especially the understanding of the heterogeneous growth of lithium, in the form of dendrites, requires a consistent model taking all mechanical effects into account. In this work, we use transition state theory based on a purely energetic concept to derive the Butler-Volmer equation for a monovalent reaction M⇌M++e− that is also consistent with the Nernst equation and discuss the energetic contribution due to deposition and stripping. With the help of the Bronsted-Evans-Polanyi principle, we generalize several approaches to include mechanical stress in the Butler-Volmer equation, discuss the underlying assumptions and suggest, through theoretical considerations, a fairly simple extended version of the Butler-Volmer equation. Beside addressing the novel aspects of the effects of mechanics, which impacts both open circuit potential and exchange current density, this work also sharpens the need for consistent use of the Butler-Volmer equation.