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Biopharmaceutical aspects of macromolecular carriers for systemic sublingual drug delivery
Berka, Pavel ; Doležal, Pavel (advisor) ; Kubová, Kateřina (referee) ; Kvítek, Libor (referee)
Charles University, Faculty of Pharmacy in Hradec Králové Department of Pharmaceutical Technology Candidate Mgr. Pavel Berka Supervisor Doc. RNDr. Pavel Doležal, CSc. Title of Doctoral Thesis Biopharmaceutical aspects of macromolecular carriers for systemic sublingual drug delivery The primary aim of this work was to experimentally verify the hypothesis on sublingual permeation of macromolecules as drug carriers. Literature data about the sublingual route of drug administration and methods of sublingual and buccal membrane processing for in vitro experiments were reviewed for this purpose. The task to design and verify a new methodology of processing and preservation of sublingual membranes suitable for permeation experiments resulted from this literature review. The new methodology of the "flash freezing" membranes uses the prepared membranes with complete epithelial composition, including the lamina propria and part of the fibrous substrate. Rapid membrane freezing with liquid nitrogen (-180 řC) was performed without cryoprotectants to avoid affecting membrane permeability, with only preliminary fixation of protein structures with sodium azide. For comparison, membranes were also frozen by conventional slow freezing to -20 řC and declared as "frozen" membranes. Neither "fresh" nor "flash frozen"...
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Synthesis and evaluation of transdermal drug permeation enhancers
Kopečná, Monika ; Vávrová, Kateřina (advisor) ; Doležal, Pavel (referee) ; Hampl, František (referee)
Penetration enhancers are compounds that facilitate transdermal drug delivery, which is an advantageous pathway of drug administration (compared to conventional methods). However, skin acts as formidable barrier enabling terrestrial life by protecting the inner body from the environmental conditions, microbes and substances. Thus, for drug administration via this pathway, some approach to temporary increase the skin permeability (e.g. permeation enhancer) should be employed. Despite the existence of many enhancer classes, there is still a need for new compounds enhancing broader spectrum of drugs, with reversible mode of action and better safety profile. One of the promising approaches is to explore natural compounds with low toxicity and irritation potential. In this thesis, I first studied various glucose and galactose derivatives bearing structural fragments that were responsible for enhancing activity of previously studied enhancers (e.g. amino acid derivatives, fatty acids and alcohols, modified ceramides). A detailed examination of these sugar- based compounds revealed potent glucoside and galactoside enhancers (12Glc6N and A15) comparable to or better than Span 20 with reversible mode of action and acceptable toxicity on keratinocyte and fibroblast cell lines. Another part of my work builds...
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Processing of Mg-based powder materials by SPS method
Moleková, Kristína ; Pacal, Bohumil (referee) ; Doležal, Pavel (advisor)
Diploma thesis occupy with preparation of porous material from magnesium powder with a HAp admixture by cold pressing followed by spark plasma sintering (SPS). This thesis contain both preparation of bulk material, diffusion plot and charakterization of materials based on the compaction process conditions. On the basis of physical mechanical characteristics, the impact of the pressing process on the subsequent sintering and the resulting material properties are evaluated. Bulk material is characterized considering to structure and physical–mechanical properties. Properties of final metarial will serve to optimize conditions for process of bulk material preparation.
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Manufacture of knives and their heat treatment
Bukvic, Tomáš ; Doležal, Pavel (referee) ; Němec, Karel (advisor)
This bachelor thesis deals with manual small series production of knives. It presents an overview of used cutlery steels and ushers their characteristics. It deals with the choice of blade geometry and material for a particular knife application. Furthermore, it initiates into the issue of heat treatment of knives, which is absolutely necessary for their functionality. The conclusion includes the documentation of the kitchen knife manufacturing process, which was made for the purpose of this thesis.
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Powder metalurgically prepared materials based on Zn and Ca
Morcinek, Tomáš ; Hasoňová, Michaela (referee) ; Doležal, Pavel (advisor)
The topic of this bachelor thesis is a process of preparation and characterization of bulk material from zinc and calcium powder mixture by hot pressing. Materials thus prepared were evaluated in terms of their microstructure and physical-mechanical properties. The influence of calcium content in the material on physical-mechanical properties of the resulting structure was observed. The solution is focused on exploration of the influence of material composition in the process of preparation of bulk material, and description of these processes from the physical-chemical point of view on the structure formation and the resulting properties of the material.
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Structure and mechanical properties of magnesium materials processed by HPT
Poloprudský, Jakub ; Němec, Karel (referee) ; Doležal, Pavel (advisor)
This thesis is focused on processing of pure magnesium by high pressure torsion method (HPT). This process belongs to the group of intensive plastic deformation methods (SPD). SPD methods are in the centre of scientific interest for several decades. Theoretical part of this thesis puts an effort to summarize basic knowledge and principles of SPD methods with extra focus on method HPT. As theoretical part continues magnesium as technical material is presented. Influence of SPD on use and properties of pure magnesium is then presented. This trend is further developed in effort to describe the effect of individual HPT process variables on the properties of pure magnesium and its alloys. Focus of practical part of this thesis is in influence of number of revolutions. Samples were processed at 1/8, 1/4, 1/2, 1, 4 and 8 turns at room temperature. Speed of process was 1rpm and applied pressure was 6 GPa. The structure of commercially pure magnesium prepared by casting and moulding were observed with focus on differences caused by input material. The structure was observed by both light microscopy and back scattered electron diffraction (EBSD), focusing on structure development, grain size and grain orientation. Compared to other works on similar topic, the emphasis here is on observing the microhardness on the vertical edge of the sample. The hardness shows a steep increase right after 1/8 of a turn. With increasing number of turns gradual homogenization of microhardness is presented accompanied by slight decrease in microhardness. No trend in microhardness relative to the distance from anvil has occurred. Structure observed with EBSD shows a bimodal character with larger grains oriented in the same direction. The three-point bending test didn’t end up as expected, and the approach to evaluation of magnesium-based HPT needs to be re-evaluated for future work. A three-point bending test was designed for the initial assessment of the basic mechanical properties of the material.
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The DPDK DNS Probe Application Extension
Doležal, Pavel ; Kučera, Jan (referee) ; Vrána, Roman (advisor)
This master's thesis is focused on extension of the DPDK DNS Probe application that monitors DNS traffic in high speed networks. It presents framework DPDK, which can be used for fast packet processing. General architecture of the DNS system is described as well as details of its components. Basic principles of transport protocol TCP are described. It introduces an effective design and implementation of DNS packet parsing to optimize DPDK DNS Probe's performance. It also introduces a design and implementation of processing DNS messages sent over TCP for export of traffic statistics. The application's performance was tested using a high speed traffic generator Spirent.
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Characterization of unique proteins of Giardia intestinalis and their role in mitosomal biogenesis.
Zemanová, Tereza ; Doležal, Pavel (advisor) ; Rada, Petr (referee)
The unicellular parasite Giardia intestinalis is one of the organisms carrying mitochondrion-related organelle known as mitosome, which is adapted to the microaerobic lifestyle. The only known fuction of the mitosome is the synthesis of the iron-sulphur clusters. The research of the mitosomal proteome provides new information on the biogenesis and function of this unusual organelle. One of the means of the mitosome research is the analysis of the interactome of the known mitosomal proteins. The state-of- the-art method of the interactome approach is the use of the chemical crosslinking and the subsequent immunoaffinity isolation of the complexes, containing the protein of interest. In this thesis, the interactomes of GiTom40 and GiMOMP35 were characterized with the bioinformatic tools. The cellular localization of four of the chosen proteins was determined by the fluorescent microscopy. One of the proteins, the predicted dynein intermediate chain DIC6939, was phylogenetically classified as an axonemal dynein. The superresolution microsopy was utilized to observe the possible colocalization of DIC6939 with the mitosomes and blue native PAGE led to the visualization of its native complexes. In this work, the optimal conditions for DIC6939 interactome isolation were succesfully determined. The outcome...
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Inducible expression systems and their use in the study of parasitic organisms.
Horáčková, Vendula ; Doležal, Pavel (advisor) ; Fišer, Radovan (referee)
1 Abstract Inducible expression systems are systems with ability to switch expression of genes of interest on and off. Therefore, they are useful molecular tools for analysis of gene function. Nowadays, there are tens of various inducible expression systems available that differ from each other in level of regulation of gene expression, time of induction, possibilities of use, etc. This work is focused on three of them to illustrate common features of the inducible expression systems which regulate gene expression at the level of transcription. Firstly, systems based on regulation of lactose operon of Escherichia coli are mentioned. Secondly, systems which use regulatory elements of tetracycline resistance-encoding transposon Tn10 of E. coli are described. Third chapter is focused on systems regulated by agonists of ecdysone receptor. In the last chapter cases of use of inducible expression systems in the study of parasitic organisms are summarized.
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