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Polyphenols delivery by polymeric materials: challenges in cancer treatment

2017-2-3, Vittorio, Orazio, Curcio, Manuela, Cojoc, Monica, Goya, Gerardo F., Hampel, Silke, Iemma, Francesca, Dubrovska, Anna, Cirillo, Giuseppe

Nanotechnology can offer different solutions for enhancing the therapeutic efficiency of polyphenols, a class of natural products widely explored for a potential applicability for the treatment of different diseases including cancer. While possessing interesting anticancer properties, polyphenols suffer from low stability and unfavorable pharmacokinetics, and thus suitable carriers are required when planning a therapeutic protocol. In the present review, an overview of the different strategies based on polymeric materials is presented, with the aim to highlight the strengths and the weaknesses of each approach and offer a platform of ideas for researchers working in the field.

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Functionalization of Ti-40Nb implant material with strontium by reactive sputtering

2017-10-10, Göttlicher, Markus, Rohnke, Marcus, Moryson, Yannik, Thomas, Jürgen, Sann, Joachim, Lode, Anja, Schumacher, Matthias, Schmidt, Romy, Pilz, Stefan, Gebert, Annett, Gemming, Thomas, Janek, Jürgen

Background: Surface functionalization of orthopedic implants with pharmaceutically active agents is a modern approach to enhance osseointegration in systemically altered bone. A local release of strontium, a verified bone building therapeutic agent, at the fracture site would diminish side effects, which could occur otherwise by oral administration. Strontium surface functionalization of specially designed titanium-niobium (Ti-40Nb) implant alloy would provide an advanced implant system that is mechanically adapted to altered bone with the ability to stimulate bone formation. Methods: Strontium-containing coatings were prepared by reactive sputtering of strontium chloride (SrCl2) in a self-constructed capacitively coupled radio frequency (RF) plasma reactor. Film morphology, structure and composition were investigated by scanning electron microscopy (SEM), time of flight secondary ion mass spectrometry (ToF-SIMS) and X-ray photoelectron spectroscopy (XPS). High-resolution transmission electron microscopy (HR-TEM) was used for the investigation of thickness and growth direction of the product layer. TEM lamellae were prepared using the focused ion beam (FIB) technique. Bioactivity of the surface coatings was tested by cultivation of primary human osteoblasts and subsequent analysis of cell morphology, viability, proliferation and differentiation. The results are correlated with the amount of strontium that is released from the coating in biomedical buffer solution, quantified by inductively coupled plasma mass spectrometry (ICP-MS). Results: Dense coatings, consisting of SrOxCly, of more than 100 nm thickness and columnar structure, were prepared. TEM images of cross sections clearly show an incoherent but well-structured interface between coating and substrate without any cracks. Sr2+ is released from the SrOxCly coating into physiological solution as proven by ICP-MS analysis. Cell culture studies showed excellent biocompatibility of the functionalized alloy. Conclusions: Ti-40Nb alloy, a potential orthopedic implant material for osteoporosis patients, could be successfully plasma coated with a dense SrOxCly film. The material performed well in in vitro tests. Nevertheless, the Sr2+ release must be optimized in future work to meet the requirements of an effective drug delivery system.

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A size dependent evaluation of the cytotoxicity and uptake of nanographene oxide

2015, Mendes, Rafael Gregorio, Koch, Britta, Bachmatiuk, Alicja, Ma, Xing, Sanchez, Samuel, Damm, Christine, Schmidt, Oliver G., Gemming, Thomas, Eckert, Jürgen, Rümmeli, Mark H.

Graphene oxide (GO) has attracted great interest due to its extraordinary potential for biomedical application. Although it is clear that the naturally occurring morphology of biological structures is crucial to their precise interactions and correct functioning, the geometrical aspects of nanoparticles are often ignored in the design of nanoparticles for biological applications. A few in vitro and in vivo studies have evaluated the cytotoxicity and biodistribution of GO, however very little is known about the influence of flake size and cytotoxicity. Herein, we aim at presenting an initial cytotoxicity evaluation of different nano-sized GO flakes for two different cell lines (HeLa (Kyoto) and macrophage (J7742)) when they are exposed to samples containing different sized nanographene oxide (NGO) flakes (mean diameter of 89 and 277 nm). The obtained data suggests that the larger NGO flakes reduce cell viability as compared to smaller flakes. In addition, the viability reduction correlates with the time and the concentration of the NGO nanoparticles to which the cells are exposed. Uptake studies were also conducted and the data suggests that both cell lines internalize the GO nanoparticles during the incubation periods studied.

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Supervised discriminant analysis for droplet micro-magnetofluidics

2015, Lin, Gungun, Fomin, Vladimir M., Makarov, Denys, Schmidt, Oliver G.

We apply the technique of supervised discriminant analysis (SDA) for in-flow detection in droplet-based magnetofluidics. Based on the SDA, we successfully discriminate bivariant droplets of different volumes containing different encapsulated magnetic content produced by a GMR-based lab-on-chip platform. We demonstrate that the accuracy of discrimination is superior when the correlation of variables for data training is included to the case when the spatial distribution of variables is considered. Droplets produced with differences in ferrofluid concentration of 2.5 mg/ml and volume of 200 pl have been identified with high accuracy (98 %), indicating the significance of SDA for e.g. the discrimination in magnetic immuno-agglutination assays. Furthermore, the results open the way for the development of a unique magnetofluidic platform for future applications in multiplexed droplet-based barcoding assays and screening.

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Single pairing spike-timing dependent plasticity in BiFeO3 memristors with a time window of 25 ms to 125 μs

2015, Du, Nan, Kiani, Mahdi, Mayr, Christian G., You, Tiangui, Bürger, Danilo, Skorupa, Ilona, Schmidt, Oliver G., Schmidt, Heidemarie

Memristive devices are popular among neuromorphic engineers for their ability to emulate forms of spike-driven synaptic plasticity by applying specific voltage and current waveforms at their two terminals. In this paper, we investigate spike-timing dependent plasticity (STDP) with a single pairing of one presynaptic voltage spike and one post-synaptic voltage spike in a BiFeO3 memristive device. In most memristive materials the learning window is primarily a function of the material characteristics and not of the applied waveform. In contrast, we show that the analog resistive switching of the developed artificial synapses allows to adjust the learning time constant of the STDP function from 25 ms to 125 μs via the duration of applied voltage spikes. Also, as the induced weight change may degrade, we investigate the remanence of the resistance change for several hours after analog resistive switching, thus emulating the processes expected in biological synapses. As the power consumption is a major constraint in neuromorphic circuits, we show methods to reduce the consumed energy per setting pulse to only 4.5 pJ in the developed artificial synapses.