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Rheological properties of gelatin-based gels for ultrasound brain phantom
Bojňanská, Terézia Marianna ; Šnejdrová, Eva (advisor) ; Holas, Ondřej (referee)
CHARLES UNIVERSITY IN PRAGUE FACULTY OF PHARMACY IN HRADEC KRALOVE DEPARTMENT OF PHARMACEUTICAL TECHNOLOGY Author: Terezia Marianna Bojnanska Supervisor: PharmDr. Eva Snejdrova, Ph.D. Title of diploma thesis: Rheological properties of gelatin-based gels for ultrasound brain phantom The diploma thesis deals with the evaluation of the viscoelastic properties of gelatin gels modified by addition of glutaraldehyde and glycerol using a rheometer with goal to verify the suitability of tested materials for their intended use as ultrasound brain phantoms. The theoretical part deals with gels in general and is focused on gelatin gels as a possible basic component of ultrasound phantoms, and the possibilities of characterizing gels as viscoelastic systems using methods of oscillatory rheometry. Gelatin gels of different concentrations (5; 7,5 and 10%) with the addition of glutaraldehyde and glycerol were characterized by complex modulus, complex viscosity, yield stress, phase angle. Temperature stability of the samples in the range from 20 to 50řC was tested. All tested gels were viscoelastic solids with a clearly defined linear-viscoelastic region, which is confirmed by phase angle values close to 0ř. With the increasing concentration of gelatin the values of the complex modulus increased, increasing...
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Development of material for agar-based ultrasound brain phantom
Řehořková, Petra ; Smékalová, Monika (advisor) ; Holas, Ondřej (referee)
Charles University, Faculty of Pharmacy in Hradec Králové Department of: Pharmaceutical technology Mentor: Mgr. Monika Smékalová, Ph.D. Consultant: MUDr. Michael Bartoš Student: Petra Řehořková Title of Thesis: Development of material for agar-based ultrasound brain phantom This thesis is concerned with the development of a material for an agar-based ultrasound phantom that would provide skill acquisition and experience in a manner approximating real surgery. The aim is to formulate and optimize the agar hydrogel preparation procedure, evaluate its acoustic properties and water loss during storage. A dependence was found between the amount of water evaporated during storage (4 weeks at 37 řC) and the glycerol content, which slows down the water loss from the samples in direct proportion. Based on the results, an agar gel (AG) formulation with 1% agar and 60% glycerol was selected for the acoustic properties measurements. During this experiment the microbial stability of AG was confirmed. The results of acoustic parameters measurements were evaluated, namely, speed of the ultrasound, attenuation coefficient and echogenicity of the samples as a function of content of scattering particles Al2O3 and SiC. It was shown that each type of particles affects grayscale value and attenuation coefficient in a...
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Polymeric particles for targeted drug delivery into mononuclear phagocytic system
Prošková, Denisa ; Holas, Ondřej (advisor) ; Šnejdrová, Eva (referee)
Charles University, Faculty of Pharmacy in Hradec Králové Department of Pharmaceutical Technology Supervisor: PharmDr. Ondřej Holas, Ph.D. Consultant: Dmytro Iefremenko, M.Sc. Student: Denisa Prošková Title of Thesis: Polymeric paticles for targeted drug delivery into mononuclear fagocytic system Polymeric nanoparticles (NPs) can act as drug nanocarriers. They are frequently used to enhance distribution to a target tissues in which they specifically act. The mononuclear phagocytic system (MPS) represents a target to which NPs could be specifically distributed. It has been found that cells of this system are involved in the development of a number of diseases. Optimal parameters of NPs suitable for MPS targeting are size ranging between 100 nm and 300 nm and negative surface charge. In this work the polymeric nanoparticles with encapsulated cholic acid were prepared by nanoprecipitation method using five selected types of non-ionic surfactants in concentration of 0,1%, 0,5%, 1% and 2%. PLGA was the polymer used for their preparation because of its high biocompatibility and biodegradability. Encapsulation efficiency, size and zeta-potential were selected as critical parameters chosen for prepared nanoparticles. The obtained data were used to characterize the effect of non-ionic surfactants on the...
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Polymeric particles for targeted and enhanced bioavailability
Kozáčková, Daniela ; Holas, Ondřej (advisor) ; Svačinová, Petra (referee)
7 ABSTRACT Charles University in Prague, Faculty of Pharmacy in Hradec Králové Department of: Pharmaceutical Technology Mentor: PharmDr. Ondřej Holas, Ph.D. Consultant: Mgr. Barbora Boltnarová Student: Daniela Kozáčková Title of thesis: Polymeric particles for targeted and enhanced bioavailability Nanoparticles prepared from biodegradable and biocompatible polymers are useful for targeted therapy of inflammatory diseases and increase the bioavailability of poorly water-soluble anti-inflammatory drugs. Targeted distribution is mainly mediated by the physico-chemical properties of nanoparticles. This can reduce unwanted side effects of encapsulated drug. The ideal properties of nanoparticles for passive targeting to cells of the mononuclear phagocytic system (MPS) are size in the range of 100 nm to 300 nm, hydrophobic character and negative surface charge. Matrix-type polymeric nanoparticles were prepared. Prepared nanoparticles were evaluated for size, polydispersity index, zetapotential and encapsulation efficiency of the drug. Three anti-inflammatory substances with different water solubility - a dexamethasone, a dexamethasone acetate and a curcumin were encapsulated. The matrix of nanoparticles was made of PLGA copolymer, three types of PLGA with different lactide:glycolide ratio were used. Nanoparticles...
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Formulation, characterization and skin application of Imiquimod loaded liposomes in combination with dendrimers
Trecáková, Viktória ; Paraskevopoulos, Georgios (advisor) ; Holas, Ondřej (referee)
Charles University, Faculty of Pharmacy in Hradec Králové Department of Pharmaceutical Technology Supervisor: Dr. Georgios Paraskevopoulos, Ph.D. Consultant: Eleni Panoutsopoulou Author: Viktória Trecáková Title of thesis: Formulation, characterization, and skin application of Imiquimod loaded liposomes in combination with dendrimers The skin barrier formed in the uppermost skin layer by the stratum corneum - among many functions - restricts the penetration of drugs through the epidermis. Nanoparticles such as liposomes and dendrimers, used for (trans) dermal drug delivery, offer a solution how to overcome this limitation. Conventional liposomes with an encapsulated drug have proven increased effectiveness and prolonged drug release for local drug delivery across intact skin in comparison to free drug. In order to increase the effectiveness of liposomes, their combination with different delivery systems has been suggested. In this study, Imiquimod was loaded to liposomes in the presence of different generations of in-house synthesized dendrimers forming novel advanced drug delivery nanosystems (aDDnSs). After an ex vivo permeation experiment on human skin, the lower generation of dendrimers was found to act synergistic with liposomes and delivered more active substance to the epidermis, while...
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Cholinesterases inhibited by novichok agents - in silico study of reactivation possibilities
Večeřa, Zbyněk ; Roh, Jaroslav (advisor) ; Holas, Ondřej (referee)
Title: Cholinesterases inhibited by novichok agents - in silico study of reacti- vation possibilities Author: Zbyněk Večeřa Department: Department of Organic and Bioorganic Chemistry Supervisor: doc. PharmDr. Jaroslav Roh, Ph.D. Advisor: PharmDr. Mgr. Tomáš Kučera, Ph.D. Abstract: Substances known as Novichok agents are banned chemical warfare agents, which were developed in Soviet Union between the 1970s and the 1980s. They were brought to the public attention very recently - they were used to po- ison a double agent named Skripal in 2018 and again in 2020 to poison Russian politician Navalny. It is the 4th generation of nerve agents which cause cholinergic syndrome by irreversible inhibition of acetylcholinesterase (AChE), manifesting symptoms such as depression of bronchial tubes, cramps or even paralysis of re- spiratory muscles and depression of the respiratory control centre in the brain. Victim then dies of asphyxiation unless antidotes are administered as soon as possible. Treatment of nerve agents induced poisoning is based on reactivating AChE by oxime compounds which bind themselves with the toxic substance by nucle- ophilic attack on electropositive point of the nerve agent, releasing acetylcholi- nesterase that can continue with function of acetylcholine hydrolysis. The task was to...
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Interaction of small molecules with proteins in silico
Kučera, Tomáš ; Korábečný, Jan (advisor) ; Jampílek, Josef (referee) ; Holas, Ondřej (referee)
Computational methods are increasingly used in biomedical research, including toxi- cological research. They are used to search for new molecules for a particular phar- macological target or to optimize the properties of known active molecules. The main methods used in these areas are molecular docking and molecular dynamics. New reactivators of butyrylcholinesterase inhibited by nerve agents were sought by methods of virtual screening. This reactivators would be applicable in prophylaxis and therapy of nerve agents poisonings. By combining the techniques of semi-flexible and flexible docking, two new structures were proposed that should specifically re- activate the inhibited butyrylcholinesterase. In addition, a virtual screening of cyclophilin D inhibitors was performed. These compounds could be used as drugs for Alzheimer's disease. Based on the availability of a huge number of crystallographic data, we decided to use a pharmacophore for the primary screening of a large database of small molecules. Molecular docking was employed in the second search phase. At the same time, we focused on the physicochemical properties of molecules. Four ligands have been found that should be inhibitors of cyclophilin D bioavailable in the central nervous system. Flexible molecular docking was used to optimize the...
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Rheological properties of gels
Korpasová, Marie ; Šnejdrová, Eva (advisor) ; Holas, Ondřej (referee)
6 2. ABSTRACT CHARLES UNIVERSITY Faculty of Pharmacy in Hradec Králové Department of Pharmaceutical Technology Name and surname: Marie Korpasová Title of Rigorous Thesis: Rheological properties of gels Supervisor: PharmDr. Eva Šnejdrová, Ph.D. Rigorous work deals with the evaluation of viscoelastic properties of gels for the formulation of brain phantoms. The theoretical part of the work characterizes brain models for training ultrasound-guided operations. Materials suitable for phantoms are presented. Furthermore, the principle of evaluation of oscillation tests performed in the experimental part is described. Agar and gelatin gels with added glutaraldehyde and glycerol were evaluated. The following parameters were used to characterize and compare the formulated gels: complex modulus G* (Pa), phase angle (ř), stress ' (Pa). The gel structure was proven for all gels tested. For gelatin gels, the gel point is indicated at a stress approximately 100 times higher than for agar gels. It can be stated that the structure of gelatin gels is significantly stronger than the structure of agar gels. A stress 10 times lower than that of gelatin gels is sufficient to destroy the structure of the agar gels and induce flow. The thermal stability of the structure of agar and gelatin gels in the temperature range 20 ř C...
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Formulation, characterization and skin application of Imiquimod loaded liposomes in combination with dendrimers
Trecáková, Viktória ; Paraskevopoulos, Georgios (advisor) ; Holas, Ondřej (referee)
Charles University, Faculty of Pharmacy in Hradec Králové Department of Pharmaceutical Technology Supervisor: Dr. Georgios Paraskevopoulos, Ph.D. Consultant: Eleni Panoutsopoulou Author: Viktória Trecáková Title of thesis: Formulation, characterization, and skin application of Imiquimod loaded liposomes in combination with dendrimers The skin barrier formed in the uppermost skin layer by the stratum corneum - among many functions - restricts the penetration of drugs through the epidermis. Nanoparticles such as liposomes and dendrimers, used for (trans) dermal drug delivery, offer a solution how to overcome this limitation. Conventional liposomes with an encapsulated drug have proven increased effectiveness and prolonged drug release for local drug delivery across intact skin in comparison to free drug. In order to increase the effectiveness of liposomes, their combination with different delivery systems has been suggested. In this study, Imiquimod was loaded to liposomes in the presence of different generations of in-house synthesized dendrimers forming novel advanced drug delivery nanosystems (aDDnSs). After an ex vivo permeation experiment on human skin, the lower generation of dendrimers was found to act synergistic with liposomes and delivered more active substance to the epidermis, while...
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Polymeric particles for targeted drug delivery into mononuclear phagocytic system
Prošková, Denisa ; Holas, Ondřej (advisor) ; Šnejdrová, Eva (referee)
Charles University, Faculty of Pharmacy in Hradec Králové Department of Pharmaceutical Technology Supervisor: PharmDr. Ondřej Holas, Ph.D. Consultant: Dmytro Iefremenko, M.Sc. Student: Denisa Prošková Title of Thesis: Polymeric paticles for targeted drug delivery into mononuclear fagocytic system Polymeric nanoparticles (NPs) can act as drug nanocarriers. They are frequently used to enhance distribution to a target tissues in which they specifically act. The mononuclear phagocytic system (MPS) represents a target to which NPs could be specifically distributed. It has been found that cells of this system are involved in the development of a number of diseases. Optimal parameters of NPs suitable for MPS targeting are size ranging between 100 nm and 300 nm and negative surface charge. In this work the polymeric nanoparticles with encapsulated cholic acid were prepared by nanoprecipitation method using five selected types of non-ionic surfactants in concentration of 0,1%, 0,5%, 1% and 2%. PLGA was the polymer used for their preparation because of its high biocompatibility and biodegradability. Encapsulation efficiency, size and zeta-potential were selected as critical parameters chosen for prepared nanoparticles. The obtained data were used to characterize the effect of non-ionic surfactants on the...
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