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Zuzana Skubalova,1,2 Simona Rex,1,2 Martina Sukupova,1 Martin Zahalka,1 Petr Skladal,3 Jan Pribyl,3 Hana Michalkova,1,2 Akila Weerasekera,4 Vojtech Adam,1,2 Zbynek Heger1,2 1Department of Chemistry and Biochemistry, Mendel University in Brno, Brno, Czech Republic; 2Central European Institute of Technology, Brno University of Technology, Brno, Czech Republic; 3Central European Institute of Technology, Masaryk University, Brno, Czech Republic; 4Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA, USACorrespondence: Zbynek HegerDepartment of Chemistry and Biochemistry, Mendel University in Brno, Zemedelska 1, Brno CZ-613 00, Czech RepublicTel +420-5-4513-3350Fax +420-5-4521-2044Email heger@mendelu.czIntroduction: The present study reports on examination of the effects of encapsulating the tyrosine kinase inhibitors (TKIs) vandetanib and lenvatinib into a biomacromolecular ferritin-based delivery system.Methods: The encapsulation of TKIs was performed via two strategies: i) using an active reversible pH-dependent reassembly of ferritin´s quaternary structure and ii) passive loading of hydrophobic TKIs through the hydrophobic channels at the junctions of ferritin subunits. After encapsulation, ferritins were surface-functionalized with folic acid promoting active-targeting capabilities.Results: The physico-chemical and nanomechanical analyses revealed that despite the comparable encapsulation efficiencies of both protocols, the active loading affects stability and rigidity of ferritins, plausibly due to their imperfect reassembly. Biological experiments with hormone-responsive breast cancer cells (T47-D and MCF-7) confirmed the cytotoxicity of encapsulated and folate-targeted TKIs to folate-receptor positive cancer cells, but only limited cytotoxic effects to healthy breast epithelium. Importantly, the long-term cytotoxic experiments revealed that compared to the pH-dependent encapsulation, the passively-loaded TKIs exert markedly higher anticancer activity, most likely due to undesired influence of harsh acidic environment used for the pH-dependent encapsulation on the TKIs’ structural and functional properties.Conclusion: Since the passive loading does not require a reassembly step for which acids are needed, the presented investigation serves as a solid basis for future studies focused on encapsulation of small hydrophobic molecules.Keywords: drug delivery, nanomedicine, lenvatinib, vandetanib

Main aim of this article is description of weld line influence on mechanical properties of plastic parts. Special design of mold was created for this research. This mold is able to create specimens with and without weld lines. These specimens undergone tensile test according standard ASTM D638 with different results. Strength and strain results were compared for both types of specimens. Nylon PA6 without any internal reinforcement was used as reference material during testing. Both specimens were investigated also by microscope in order to see composition of weld line and plastic material. Microstructure showed geometry of weld line and also fracture surfaces indicated presence of plastic deformation

Main aim of this article and research is to describe exact influence of key parameter in injection molding process. This key parameter is temperature. Nowadays is possible to use wide range of advanced virtual simulation tools, which were in research used. Article is focused on determining optimal temperature of injected plastic material, temperature of mold and temperature of coolant. For veryfing of virtual method was performed real injection molding with same input parameters and results were compared. For evaluating of achieved quality was investigated influence on whole molding process and influence on final product properties. As testing material was choosen High-Density Polyethylene with properties described in article.

The paper deals with the software DEFORM, which is used for forming simulations at the Regional Technological Institute in University of West Bohemia in Pilsen, and with the issue of acquisition and validation of material data. Material library is an essential part of a software, but sometimes it is necessary to add individual material into the library or edit existing materials to improve their description. The article describes the real material tests and individual parameters that should be considered during material description. Further is shown data conversion for virtual simulations in DEFORM software. At the end, the verification of material description is shown. It is done by the comparing of results given by virtual simulation and by the real forming process. The whole procedure of new material description is shown on the brass CuZn30. Material description is deeply described in this paper.

Hlavním cílem tohoto článku je popis viskozity a chování materiálu PA 6 se skelnými vlákny při plnění. Vstřikování plastů je jednou z nejčastěji používaných výrobních metod. Kvalita výsledného produktu je spojena s nastavenými parametry vstřikovacího procesu. Je nutné správně pochopit proces plnění formy a proto byl proveden tento výzkum. Spirálový test zatékavosti byl proveden, proto aby byly zjištěny vlivy různých parametrů na celkové plnění formy. Jako výsledný parametr byla srovnána celková délka spirály. Testovaný materiál byl PA6 s 15% skelných vláken (výrobní název Durethan BKV 15). Pro validaci byly provedeny virtuální simulace. Byla zjištěna lineární závislost mezi stupňem naplnění a ostatními parametry. Pro tento test byla navržena a vyrobena speciální forma. The main aim of this paper was to describe the viscosity and injection mold filling behavior of PA6 with 15% of glass fibers. Injection molding is one of the most widely used processes for polymer products. The quality of these products is directly linked to correct choice of process parameters. It is necessary to understand the filling behavior of the polymer material during the injection molding process. The spiral flow test was carried out in this study to explore the effects of several injection process parameters. The resulting lengths of spiral flow were compared. The polymer material under test was Polyamide 6 with 15% of short glass fibers (trade name: Durethan BKV 15). Virtual testing as well as real testing was performed. A predominantly linear relationship between the flow length and the mold temperature, melt temperature and injection pressure is described here. A special mold was designed for this test.

This article deals with the influence of the gate position on the final properties of a plastic product after the injection moulding process. Parameters such as temperature, fibre orientation and filling velocity are evaluated. The importance of the internal fibre orientation on the mechanical properties is also described. Advanced virtual mould-flow analysis is used for this research. A simple brick from Polybutylene Terephthalate (PBT) with 30% of short glass fibres is chosen as the reference part. A virtual model of PBT is described in depth in this article. An injection process with the same initial parameters was used for three different locations of the pin gate. This type of gate is considered because it is one of the most frequently used in the plastics industry. Different kinds of gates and their influence on filling are also briefly described. This paper shows the importance of the gate location and it also helps to understand the flow of short fibre reinforced thermoplastics inside the mould cavity. The article presents an in-depth and complex view of the issue of mould filling.

This article explores the influence of production technique on the strength of nylon parts. Identical specimens were manufactured by various techniques. The material of specimens was nylon PA6. 3D printing and injection molding were used, with various orientations of printed layers, and various orientations of specimens in the working space of the 3D printer. The variants are described in detail. A special mold was used for the injection molding process in order to make specimens with and without a weld line. The effect of this weld line was evaluated. All specimens were tested using the standard tensile test configuration. The strength was compared. It was found that the same plastic material has very different mechanical properties depending on the production process.

Dynamic behavior of the forging machines is necessary to explore due to the increasing of speeds on large forging hydraulic presses for open die forging. The paper describes the modal analysis of two selected presses, which represent the most common designs of hydraulic presses for forging. The first press is with double-column frame CKV 50 with the force 50MN and the second one is with four-column frame CKV 170 with the force 170 MN. Further are described the simulations of oscillation, which was excited by time-dependent work force. Results of analysis are compared with measurement in the real operation.

This paper deals with the possibilities of advanced FEM simulations used for the understanding of process of loading of crank presses. Concrete example presents transient (time-dependent) dynamic simulation loading. Load input parameters of forging press are determined from simulation of technological operation of forming. Results of virtual simulations are compared with standard analytical calculations.