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PhD topics for academic year 2021/2022

Department of Chemical Engineering

Synthesis and Production of Drugs - Drugs and Biomaterials

Faculty of Chemical Engineering

Advanced formulation approaches for topical delivery

Štěpánek František, prof. Ing. Ph.D. ( Fra...@vscht.cz)
Zbytovská Jarmila, doc. Mgr. Dr.rer.nat. ( zby...@vscht.cz)
Although skin appears to be a macroscopically homogeneous and biologically passive structure, it is exactly the opposite: it is incredibly heterogeneous both chemically and structurally, and it is host to a diversity of active cells such as macrophages and bacteria. Traditional approaches to topical delivery have relied on relatively simple systems such as passive diffusion from water- or oil-based solutions or creams/gels. The aim of this project is to investigate bioactive transport as a mechanism for topical delivery and find a solution to such molecules as therapeutic peptides, which are known to be extremely challenging to formulate and delivery to the body. This project will explore the use of drug delivery systems that are actively phagocytised for targeting macrophages residing in the skin. These drug delivery systems will include naturally sourced polysaccharide shells or lipidic vesicles obtained from single-cell organisms. Their mild immunogenicity, biocompatibility and ability to encapsulate a broad range of molecules will be utilized for the formulation of APIs that have proven to be challenging by traditional means.
Faculty of Chemical Engineering

Design and application of supra-lipidic structures

Štěpánek František, prof. Ing. Ph.D. ( Fra...@vscht.cz)
Lizoňová Denisa, Ing. ( den...@gmail.com)
The gastro-intestinal transit, emulsification, digestion and absorption of lipidic components from food is crucial not only from the nutritional point of view but also for the dissolution and absorption of many drugs, and therefore their bioavailability. An increasing number of active pharmaceutical ingredients (APIs) that enter the drug development process are highly lipophilic, which makes their bioavailability susceptible to patient-specific dietary habits and often leads to undesired phenomena such as positive food effect. For some APIs, the bioavailability can be up to five times higher when taken on a full stomach compared to bioavailability in the fasted state. The aim of this project is to develop a formulation platform that would make the dissolution, absorption and pharmacokinetics of lipophilic APIs independent of food intake, while not containing a large amount of lipids in the formulation itself. The idea is to create particles that “look like lipids” on the outside but their volume contains predominantly the API or other excipients. Such structures can include e.g. drug suspensions encapsulated in giant liposomes or their aggregates, drug nanocrystals coated by a phospholipid monolayer, or drug-loaded mesoporous silica particles encapsulated within a lipid bi-layer. These elementary structures can also be combined, carrying e.g. several different APIs, functional excipients for absorption enhancement, or pH modifiers that can further reduce patient-to-patient variability.
Faculty of Chemical Engineering

Development of nanoparticles for drug delivery in wound healing

Šoóš Miroslav, prof. Ing. Ph.D. ( Mir...@vscht.cz)
Main focus of this project is to synthesize multifunctional vesicles loaded with hydrophilic and hydrophobic drugs to be used in wound healing. Since these particles can be used directly or as an intermediate during skin dressing their detailed characterization and colloidal stability will be essential. Student will study the impact of vesicle composition (primary system will be surfactant and cholesterol forming niosomes) and method of preparation on the size and properties of the formed nano carriers as well as drug encapsulation efficiency. Once drug will be loaded into vesicles the release kinetics will be measured as a function of molecular weight of used surfactants and ionic strength. Quality of the prepared samples will be characterized by combination of analytical techniques including 3D modulated DLS, Depolarized DLS, static light scattering, optical video microscopy combined with image analysis and cryo-TEM. While batch production mode is simple to realize, part of the project will be also preparation of multifunctional vesicles in microfluidic systems and compare their properties with batch production method.
Faculty of Chemical Engineering

Development of 3D cell cultures for the evaluation of drug delivery systems

Štěpánek František, prof. Ing. Ph.D. ( Fra...@vscht.cz)
Faculty of Chemical Engineering

Erosion-controlled drug release from super-placebo tablets

Štěpánek František, prof. Ing. Ph.D. ( Fra...@vscht.cz)
The rate of drug release from a pharmaceutical tablet is one of its most important quality attributes. As an ever-increasing number of Active Pharmaceutical Ingredients (APIs) are developed in alternative solid-state forms such as metastable polymorphs, co-crystals or amorphs, it is desirable to control the rate of drug release by the properties of the tablet matrix rather than by the properties of the API itself. The aim of this project is to explore the so-called “super-placebo” concept, i.e. tablets that erode in a defined way which is independent of the API they contain. The project will systematically explore the relationship between the rate of tablet erosion, the proportion of soluble and insoluble excipients (e.g. mannitol, microcrystalline cellulose), and the manufacturing process parameters (e.g. compaction pressure). The ability to control drug release rate will be demonstrated using several real-world APIs. Advanced instrumental methods such as Magnetic Resonance Imaging, x-ray micro CT and high-speed video-imaging will be used in order to gain a deep understanding of the underlying tablet erosion mechanisms.
Faculty of Chemical Engineering

Formulation and bioavailability of natural poly-actives

Štěpánek František, prof. Ing. Ph.D. ( Fra...@vscht.cz)
Current paradigm in pharmaceutical drug development and its regulatory environment is based on the concept of Active Pharmaceutical Ingredient (API) as a well-defined single molecular entity that is contained in the dosage form at a precise quantity and chemical purity. Although rational in many ways, this approach is rather different from evolution-proof substances found in Nature. The main drawback is single-API medicines is the development of drug resistance over historically extremely short time periods (only a few decades), which is problematic not only in the area of antibiotics but also in cancer treatment, anti-fungal and various anti-parasitic drugs that gradually lose their effectiveness. In contrast, there are examples of natural systems that maintain their efficacy for many millennia. Perhaps the most prominent example of such material is bee propolis. Chemically, propolis is a mixture of several hundred chemical species with location- and season-dependent composition, which would completely disqualify it as a registered medicinal substance. However, it is exactly this variable multi-component character that makes is so robust and durable, not giving pathogens a chance to develop resistance. Propolis contains both water-soluble and water-insoluble components and is typically applied as ethanol dispersion only for surface treatment. The aim of this project is to explore formulation approaches that could enable oral administration of propolis and ensure its safety and bioavailability. The project is multidisciplinary and will include not only formulation and analytical work, but also in vitro and in vivo testing of biological efficacy.
Faculty of Chemical Engineering

High-throughput development and continuous manufacturing of SMEDD systems

Štěpánek František, prof. Ing. Ph.D. ( Fra...@vscht.cz)
Self micro-emulsifying drug delivery systems (SMEDDS) are formulations that spontaneously form a mini- or micro-emulsion upon contact with water. They typically contain the active pharmaceutical ingredient (API), a mixture of oils or low-melting lipids in which the API is soluble, and one or more surfactants and co-surfactants. SMEDDS are complex ternary or higher-order mixtures whose phase behaviour and properties are notoriously difficult to predict at present. Therefore, the development of SMEDDS is to a large extent an empirical process. Due to a large number of formulation components and their possible ratios, it is rarely possible to completely cover the entire design space, which may lead to sub-optimum formulations or even a false rejection of a particular API as non-formulatable. The aim of this project is to construct a device and develop a methodology for automatic combinatorial screening of SMEDDS formulations and their continuous manufacturing based on the so-called liquid marbles. The project will build on a recently developed patented device called “Marblemat” and extend its capabilities towards combinatorial mixing of formulation components and serial production of liquid marbles with systematically varying composition. Simultaneously, capability for high-throughput testing of the formulation properties such as mechanical strength, temperature stability and dissolution properties will be implemented and demonstrated on several industry-relevant APIs.
Faculty of Chemical Engineering

Naturally sourced particles for drug encapsulation and delivery

Štěpánek František, prof. Ing. Ph.D. ( Fra...@vscht.cz)
Drug encapsulation into a suitable carrier particle is a common method used in situations where it is possible to either modify the surface properties (e.g. powder flowability or dispersibility in water), to protect the encapsulated component from the environment (e.g. enzymatic digestion in the GI tract) or to control the rate of drug release. Several man-made encapsulation processes are known. However, there are also many natural systems that rely on encapsulation – the cell walls of single cell organisms or their spores, natural particles such as pollen, extra-cellular vesicles, or sub-cellular structures such as vacuoles or other organelles. Some of these structures are highly specific in terms of drug diffusion and its selectivity, or in terms of recognition by cells of the immune system e.g. due to specific shape of the presence of immunomodulatory functional groups on the surface. Yeast glucan particles can serve as a prime example. The aim of this inter-disciplinary project is to investigate the potential of several different types of naturally sourced particles in drug formulation and drug delivery. Both cell-wall derived particles and organelle-based particles will be considered. Special attention will be paid to the process of particle extraction and isolation, as well to the drug encapsulation methodology.
Faculty of Chemical Engineering

Oleogels for drug delivery

Štěpánek František, prof. Ing. Ph.D. ( Fra...@vscht.cz)
Řehoř Ivan, RNDr. Ph.D. ( REH...@vscht.cz)
Oleogels, like hydrogels, are semi-solid materials that can contain up to 99 % of a liquid, which is solidified by a three-dimensional polymer network. While hydrogels contain as the liquid and the polymers are hydrophilic, oleogels contain oil and an oleophilic polymer network. Many APIs that are poorly soluble in water could potentially be formulated using oleogels and be either directly dissolved in the oil phase or form a particle depot that would dissolve in the oil gradually and act as a longer-lasting reservoir. The aim of this project is to evaluate the suitablitity of selected oleogel formulations for drug delivery applications from the point of view of manufacturability, drug release kinetics, drug stability, and biological compatibility. The application of oleogels will be demonstrated using several selected APIs both in vitro and in vivo.
Faculty of Chemical Engineering

On-line measurement and control of continuous pharmaceutical manufacturing

Štěpánek František, prof. Ing. Ph.D. ( Fra...@vscht.cz)
The manufacturing of pharmaceutical products is typically carried out batch-wise. While this makes sense for products that are manufactured only occasionally in small quantities, batch processes also have several drawbacks. These include excessive dead-times, need for cleaning to avoid cross-contamination, and generally poorer control over the product quality. By switching pharmaceutical manufacturing to a continuous mode, equipment utilisation can be increased theoretically to 100 %, the footprint of the facilities can be substantially reduced, and standard feed-back and feed-forward control schemes applied. A crucial component of continuous manufacturing processes is on-line measurement of key quality attributes such as particle size distribution, composition uniformity of granular blends, or moisture content. Advanced analytical instruments such as Near-Infrared probes can be used for this purpose. The aim of this project is to explore the on-line measurement and control methods for continuous pharmaceutical manufacturing in an industrial setting and combine them with computer simulation tools in order to optimize the overall process robustness and operability.
Faculty of Chemical Engineering

Preparation of drug delivery carriers for treatment of rheumatoid arthritis

Šoóš Miroslav, prof. Ing. Ph.D. ( Mir...@vscht.cz)
Skořepová Eliška, Ing. Ph.D. ( sko...@seznam.cz)
Rheumatoid arthritis (RA) is a chronic autoimmune disorder, mainly affecting joints that are identified by inflammation and swelling of the synovium of the joint. Today, apart from the conventional synthetic disease-modifying antirheumatic drugs (DMARDs), a number of biological DMARDs have been approved. Recently the first targeted synthetic DMARD has also been approved, while other targeted compounds are in the development phase. Particularly interesting is group of drugs which are based on gold complexes. Despite their promising properties, these drugs has low solubility in water and thus low bioavailability. Therefore, within this project we plan to investigate possibility to prepare more soluble compounds of gold complexes using crystal engineering approach as well as formulate these drugs into various nanocarriers. Combination of various preparation and analytical techniques will be used to investigate stability of gold complexes. In the next step we will investigate the impact of encapsulation matrix or complexation partner on the dissolution characteristics of gold complexes.
Faculty of Chemical Engineering

Process scale-up of pharmaceutical spray drying

Štěpánek František, prof. Ing. Ph.D. ( Fra...@vscht.cz)
Spray drying is versatile method for converting solutions, suspensions or pastes into dry, free-flowing powders in the pharmaceutical, food and nutraceutical industries. During product development, the formulation and process variables are typically optimised using a laboratory-scale spray dryer, and the process is then transferred to a pilot or full manufacturing scale. However, it is notoriously difficult to maintain the same particle properties using spray dryers at different scales, which often necessitated long and expensive trials to be carried out at the large scale. The aim of this project is to develop a robust methodology for spray drying process scale-up in an industrial pharmaceutical setting. The main focus will on the transferability of particle size and particle morphology, as these two parameters are known to be the most sensitive to parameters that vary between the laboratory and the manufacturing scale spray-dryers: the initial droplet size and the drying conditions (temperature, gas flowrate, and residence time in the drying chamber).
Faculty of Chemical Engineering

Synthesis and characterisation of particles with immuno-adhesive properties

Štěpánek František, prof. Ing. Ph.D. ( Fra...@vscht.cz)
Lizoňová Denisa, Ing. ( den...@gmail.com)
The specificity of adhesion to the target cells or tissues in a physiological envirionment is a key requisite for the successful implementation of drug delivery systems (DDS). The aim of this work is to explore DDS based on immunoliposomes and their composites (e.g. with magnetic nanoparticles) using surface modification by antibody fragments and other suitable targeting moieties. The immunoliposomes will be tested both in vitro and in vivo in terms of specificity of adhesion, pharmacokinetics, and ability do encapsulate and delivery drugs or pro-drugs.
Faculty of Chemical Engineering

Synthesis and characterization of nanoparticle system for transfection of cells

Šoóš Miroslav, prof. Ing. Ph.D. ( Mir...@vscht.cz)
Delivery of gene vectors during cell transfection is commonly done by positively charged poly ions. When coupled with DNA, this method is capable to deliver the genetic information into the host cell’s nucleus resulting in the production of the protein of interest. Even though this procedure is commonly used, toxicity of polycations results in low cell viability and loss of the culture. In this project we plan to develop a transfection system based on the biodegradable polymers with low toxicity using recently developed aggregation process. Student will be involved in the selection, synthesis and modification of the biodegradable polymer followed by the preparation of polymeric nanoparticles as a DNA carriers. Properties of the prepared polymer will be characterized via various methods include light scattering or GPC. Formed nanoparticles will be characterized by DLS, SEM/TEM, measurement of zeta potential and their colloidal stability. Consequent complexation of produced NPs with DNA and their size will be tested as well. In the last part of the project, process of complexation will be scaled up to the necessary amount to be tested with living cells.

Department of Organic Chemistry

Synthesis and Production of Drugs - Drugs and Biomaterials

Faculty of Chemical Technology

Synthesis of cytochalasan analogues with antimetastatic activity

Perlíková Pavla, Mgr. et Mgr. Ph.D. ( per...@vscht.cz)
Cytochalasans are natural compounds with interesting biological activities. Binding to a barbed ends of actin microfilaments is typical for all cytochalasans. Thanks to their interference with microfilament dynamics, some of natural cytochalasans showed antimetastatic activities. Antimetastatic activity is a key feature of so called "migrastatics", a new class of potential cancer therapeutics. In this PhD thesis, new analogues of cytochalasans will be designed and synthesized based on rational drug design and structure-activity relationship study will be performed. Then, the thesis will be focused on design and synthesis of cytochalasan prodrugs with improved water solubility.
Faculty of Chemical Technology

Nanotherapeutics based on antimicrobial peptides for multiresistance bacteria species treatment

Etrych Tomáš, RNDr. Ph.D., DSc. ( etr...@imc.cas.cz)
Pola Robert, Ing. ( p...@imc.cas.cz)
The work will be focused on the study of biodegradable polymeric nanomaterials carrying antimicrobial peptides. The studied nanomaterials will have a linear, branched or star-like structure composed from hydrophilic or amphiphilic copolymers containing stimuli-sensitive linkers. The aim of this work will be to develop an effective nanotherapeutic for the treatment of infections caused by resistant bacteria. The biological activity of these polymeric nanomaterials will be studied in dependence on the detailed structure of the whole system. The student will extend his/her knowledge in the area of preparation of mentioned nanomaterials, in vitro biochemical and biological testing and in vivo biological characterization of nanomaterials. The applicant's knowledge and experience in organic and / or macromolecular chemistry is an advantage, along with the desire to learn new things in other fields, such as biochemistry. The work assumes close cooperation with cooperating biological teams in the Czech Republic and abroad.
Institute of Macromolecular Chemistry CAS

Department of Organic Technology

Synthesis and Production of Drugs - Drugs and Biomaterials

Faculty of Chemical Technology

Application of milling and co-milling processes to formulation of poorly soluble drugs

Zámostný Petr, prof. Ing. Ph.D. ( zam...@vscht.cz)
Poorly soluble drugs (BCS II and IV classes) represent an important segment of marketed drugs. Improving solubility or at least the drug release kinetics is therefore a continuing challenge, which is approached by many ways on several levels. The milling, nano-milling, and/or co-milling processes of a drug with optional other excipients provide a way how to change the phase composition of the drug, increase the specific surface of drug particles, modify that surface, and also form composite particles. This study should be aimed at the options and possibilities of improving the drug release by all the above mechanisms, especially those related to particle technology. The study should involve both the preparation of particles and their formulation into suitable dosage forms and seek optimized approaches bringing the best performance while complying with the requirements of industrial manufacturability of the formulation.
Faculty of Chemical Technology

Modeling of drug release from the solid dispersions by diffusion erosion models

Zámostný Petr, prof. Ing. Ph.D. ( zam...@vscht.cz)
This work is aimed at the study of the drug release from the solid dosage forms comprsing solid dispersions. Such formulations exhibit a well-defined structure, and the drug dissolution can be studied not only by classical dissolution techniques, but also by the apparent intrinsic dissolution. Several fronts develop in dosage forms of this type, where thos fronts corresponds to the liquid penetration, drug leaching and erosion of the residual matrix. Such processes can be described by diffusion-erosion models, which allow determining their rate controlling steps and characteristic rates to be used for the design of controlled release drugs.
Faculty of Chemical Technology

Nanoparticulate formulation approaches for topical delivery

Zbytovská Jarmila, doc. Mgr. Dr.rer.nat. ( zby...@vscht.cz)
Human skin represents a unique protecting barrier which, however, limits the trans/dermal drug delivery. Nanoparticulate systems show a great potential to improve drug permeation across the skin barrier, though their exact interaction mechanism with the skin barrier has not been fully understood yet. The aim of this work will be development and characterization of advanced nanoparticulate systems containing selected actives. Effectivity of the formulations will be determined in vitro on isolated skin or by other techniques. For deeper understanding interactions between the nanoparticles and skin barrier, biophysical techniques (e.g. infrared and Raman spectroscopy or X-ray diffraction) will be applied. The main outputs of the work will be effectivity evaluation of the particular formulation approaches and elucidating of interactions between the nanoparticles and skin barrier.

Department of Polymers

Synthesis and Production of Drugs - Drugs and Biomaterials

Faculty of Chemical Technology

Bioactive coatings promoting spontaneous endothelialization of vascular vessel grafts

Riedel Tomáš, Ing. Ph.D. ( tom...@uhkt.cz)
The surface of biomaterials that are in long-term contact with blood (e.g., vascular prostheses, stents) triggers inflammatory processes of the organism leading to activation of the coagulation cascade and formation of thrombi, and to a subsequent graft failure. The aim of this work is the development of coatings that would suppress activation of the coagulation cascade and immune response of the organism, while actively encouraging the formation of endothelium on the surface of vascular prostheses after their implantation. One approach will be based on coating the internal surface of a synthetic and decellularized vessel with a fibrin network that will be modified by bioactive molecules such as heparin, growth factors, oligosaccharides, and other bioreceptors specifically promoting the adhesion of progenitor endothelial cells. An alternative approach will be based on suppressing the unwanted body reactions by means of so-called polymer brushes and their subsequent functionalization by the above-mentioned biomolecules. We assume that, after implantation, heparin will suppresses the coagulation cascade, while the other bioactive molecules will promote endothelization of the graft by capturing progenitor endothelial cells from blood.
Institute of Macromolecular Chemistry CAS
Faculty of Chemical Technology

Biodegradable polymer systems for medical applications

Šlouf Miroslav, RNDr. Ph.D.
Biodegradable and biocompatible polymer systems show numerous applications in both human and veterinary medicine. We have recently developed and patented multiphase polymer systems based on thermoplasticized starch (TPS), polycaprolactone (PCL), titanium dioxide based nanoparticles (TiX) and antibiotics (ATB). Morphology and properties of these systems can be adjusted by their composition and targeted phase structure modification during the processing. TPS/PCL/ATB systems can be employed in treatment of strong local infections such as osteomyelitis. The project comprises preparation of the above systems (by melt mixing), optimization of their phase structure (targeted modification of processing conditions), characterization of their morphology (electron microscopy), properties (macro- and micromechanical properties), and participation in medical tests in collaboration with local hospital (FN Motol; treatment of local infects, biodegradability).
Institute of Macromolecular Chemistry CAS
Faculty of Chemical Technology

Preparation of stimuli-responsive polymer nanomedicines using microfluidic nanoprecipitation – the in vitro and in vivo performance under simulated physiological conditions

Jager Eliezer, Mgr. Ph.D. ( j...@imc.cas.cz)
Jäger Alessandro, Mgr. PhD.
Nanomedicines gain much more relevance in biomedical applications if they are tailored to be degradable in response to certain external stimuli. Such stimulus may be enzymatic removal of protecting groups, a pH change, light or the presence of reactive oxygen species (ROS) in cancer. Herein, imbalances on the cells micro-environment (pH changes, ROS production) will be explored for the synthesis of stimuli-responsive polymers and block copolymers. Inspired by the ease and effectiveness of the self-assembly of amphiphilic block copolymers in solution, several polymer nanomedicines, i.e., micelles, nanoparticles and vesicles will be designed to display tunable stimuli degradation in the presence of physiologically relevant changes in pH, temperature or ROS concentrations and will be prepared by microfluidic nanoprecipitation. This technique allows us the production of uniform particles with controllable size, shape and surface chemistry in a reproducible manner. The produced polymer self-assemblies will be characterized using standard scattering techniques (DSL/SLS/ELS, SAXS and SANS) and by microscopy. The effectiveness of the polymer nanosystems will be evaluated in in vitro and in in vivo models simulating the physiological balanced and imbalanced of the microenvironment.
Institute of Macromolecular Chemistry CAS
Faculty of Chemical Technology

Self-cleaning anti-biofilm polymer surfaces

Hrubý Martin, Mgr. Ph.D., DSc. ( mhr...@centrum.cz)
The formation of bacterial biofilms is a one of the major issues in the current biomedical research. In the body, such biofilms are created on the surface of the medical devices, e.g., joint prostheses or heart valves, where they cause inflammation and chronic infections. The aim of this Ph.D. project is to develop a novel class of smart self-cleaning anti-biofilm polymer surfaces, based on poly(2-alkyl-2-oxazoline)s, that are both anti-fouling and able to catalytically prevent the biofilm formation in the very long-term period. The project work includes polymer synthesis, the surfaces preparation and the study of their physicochemical properties. Moreover, the selected surfaces will be subjected to comprehensive in vitro and in vivo testing in the collaboration with biologists.
Institute of Macromolecular Chemistry CAS
Faculty of Chemical Technology

Stimuli-responsive supramolecular polymer systems for biomedical applications

Hrubý Martin, Mgr. Ph.D., DSc. ( mhr...@centrum.cz)
Vetrík Miroslav, Mgr. Ph.D. ( vet...@imc.cas.cz)
Self-assembly of (macro)molecules is of crucial importance in the architecture of living organisms. Supramolecular systems have their key properties critically dependent on self-assembly and find use in the area of biomedical applications especially if they are able to reversibly react to external stimuli (changes in pH, light, redox potential, ultrasound, temperature, concentration of certain substances). The doctoral thesis will be based on chemical and/or physicochemical preparation and study of self-assembly of such multi-stimuli-responsive nanoparticles with external environment (pH, redox potential and temperature responsiveness); the exact topic will take into account the student´s interests. The studied nanoparticles and injectable depot systems will be designed for diagnostics and personalized immunoradiotherapy and immunochemotherapy of cancer and autoimmune diseases. Optimized nanoparticles will be then provided to collaborating biological workplaces for in vivo testing.
Institute of Macromolecular Chemistry CAS

Department of Solid State Engineering

Synthesis and Production of Drugs - Drugs and Biomaterials

Faculty of Chemical Technology

Advanced bactericidal coatings with long-lasting effect

Siegel Jakub, doc. Ing. Ph.D. ( Jak...@vscht.cz)
Experimental work focused on the optimization of immobilization of metal nanoparticles on polymeric supports for the preparation of a new generation of antimicrobial surfaces. Nanoparticle immobilization will be acomplished by physical methods based on the interaction of prepared particles with laser radiation. Antibacterial effects and biocompatibility of developed surfaces will be evaluated in cooperation with the Department of Biochemistry and Microbiology VŠCHT Prague.
Faculty of Chemical Technology

A new generation of materials and approaches for detecting and destroying of pharmaceutical contaminants in the aquatic environment

Lyutakov Oleksiy, Mgr. Ph.D. ( ole...@vscht.cz)
Faculty of Chemical Technology

SERS and artificial neural network – toward the analysis of complex biochemical samples

Lyutakov Oleksiy, Mgr. Ph.D. ( ole...@vscht.cz)
Faculty of Chemical Technology

Smart antimicrobial materials

Švorčík Václav, prof. Ing. DrSc. ( svo...@vscht.cz)
Faculty of Chemical Technology

Smart materials for medical and biological applications

Lyutakov Oleksiy, Mgr. Ph.D. ( ole...@vscht.cz)
Faculty of Chemical Technology

New concept of enhancing targeting of polymer conjugates for drug delivery to brain

Pánek Jiří, Ing. Ph.D. ( p...@imc.cas.cz)
Štěpánek Petr, RNDr. DrSc.
The aim of the Ph.D. thesis is to develop a conceptually new system for inhibition of glutamate carboxypeptidase II (GCP II) in brain as a treatment tool for suppressing glutamate toxicity and subsequent neuroinflammation-caused secondary damage after ischemic, hemorrhagic or traumatic brain injuries (which typically damage brain and spinal cord more than the primary injury and are the reason why neural damage often gets worse within few days after first occurrence of symptoms). The delivery system will modify the unfavorably hydrophilic properties of the GCP II inhibitors, which are normally unable to cross the blood-brain barrier (BBB). The delivery system will also enhance inhibitor potency by forming multivalent physically self-assembled („molecular toolbox“) biocompatible polymer-coated solid lipid nanoparticles. The inhibitor-containing nanoparticles will decompose after crossing the BBB by apolipoprotein E-mediated transfer and the polymer-bound inhibitor will become reversibly membrane-anchored in the proximity of the membrane-bound GCP II. This membrane anchoring is expected to be a generally applicable concept for targeting also enzymes or receptors other than GCP II.
Institute of Macromolecular Chemistry CAS
Faculty of Chemical Technology

Polymer-bound reactive oxygen species precursors for cancer therapy

Vetrík Miroslav, Mgr. Ph.D. ( vet...@imc.cas.cz)
Hrubý Martin, Mgr. Ph.D., DSc. ( mhr...@centrum.cz)
Radiation therapy applies ionization radiation to cancer tissue to elicit the reactive oxygen species (ROS) production to kill the cancer cells. The radiation treatment can be boosted by application of radiosensitizers. The aim of this thesis is to prepare a polymer material that is able to deliver artificial ROS into the cancer cells or deliver precursors that will trigger the ROS generation at the place of action. Moreover, specific hypoxic markers can be utilized for active targeting to hypoxic tumor tissue. The student will design and prepare polymer systems which will be releasing ROS as: superoxide, peroxides or singlet oxygen in desired cancer site. The project is highly multidisciplinary, it includes polymer and organic syntheses, characterization techniques such as FTIR, 1-H 13-C NMR, SEC, DLS, SAXS and SANS. Moreover, the student can participate on biological studies which will be performed on collaborating workplace. If the student is interested in, it is possible to make part of the study at collaborating workplace in France within the program “double degree PhD”, the deadline is February 14, 2020 (see https://studium.ifp.cz/cz/doktorandi/barrande-fellowship-program/ ). If you are interested in this option, please contact the supervisor as soon as possible.
Institute of Macromolecular Chemistry CAS
Faculty of Chemical Technology

Polymeric nanomaterials for neoadjuvant multimodal therapy of advanced neoplastic diseases

Etrych Tomáš, RNDr. Ph.D., DSc. ( etr...@imc.cas.cz)
Kozák Ladislav, Ing.
The main aim of this work will be the development of new multi-component biocompatible and non-immunogenic polymer-based nanotherapeutics and nanodiagnostics adapted for multimodal advanced therapy of neoplastic diseases. The dissertation will be based on the preparation of new polymeric nanomaterials that will allow the controlled delivery of active therapeutic agents or tumor visualization for fluorescently navigated surgery. These nanomaterials will serve as a tool for multimodal neoadjuvant therapy based on sequential administration of chemotherapy and immunotherapy in combination with fluorescently navigated surgery. The work will focus on tailor-made solutions using covalent binding of active molecules with several functions: targeted transport of active molecules, their protection during transport against degradation and controlled release based on site-specific stimuli. The thesis will consist in the design, synthesis and study of physico-chemical and biological properties of polymeric materials. The applicant's knowledge and experience in organic or macromolecular chemistry is an advantage, along with the desire to learn new things in other fields, such as biochemistry. The work assumes close cooperation with cooperating biological teams in the Czech Republic and abroad.
Institute of Macromolecular Chemistry CAS

Department of Solid State Chemistry

Synthesis and Production of Drugs - Drugs and Biomaterials

Faculty of Chemical Technology

Growing Single Crystals and Structure Analysis of Multiple Component Crystals

Čejka Jan, Ing. Ph.D. ( cej...@vscht.cz)
API's multiple-component crystals are a valuable option in modfying pharmacokinetic profile, stability of API etc. The application properties of any particular active compound are often rendered by means of the component is built in the structure. This work aims to prepare single crystals of salts, solvates, co-crystals and polymorphs of selected compounds, study potentional temperature dependent phase transitions, their complex characterization using a bundle of analytical methods accenting X-ray structure analysis and consequent correlation of parameters and solvent occupied voids.
Faculty of Chemical Technology

Inorganic carriers of active pharmaceutical ingredients

Kovanda František, prof. Ing. CSc. ( kov...@vscht.cz)
The work is focused on development of new solid dosage forms. Release of active pharmaceutical ingredient and its stability against degradation can be considerably affected after its incorporation into a carrier. Inorganic compounds with layered structure, namely the layered double hydroxides suitable for intercalation of negatively charged anionic species, will be used as the host structures. Methods for preparation of intercalates, interactions between the host structure and drugs intercalated in interlayer, stability of intercalated drugs, and their back release in simulated body fluids will be studied.
Faculty of Chemical Technology

Pharmaceutical substances crystal structure solution by combination of data from ss-NMR, structure prediction and powder diffraction

Hušák Michal, doc. Dr. Ing. ( hus...@vscht.cz)
When we have no singe crystal diffraction data available we can solve the structure from alternative experiments. We can predict the structure and confirm the prediction by experimental and theoretical ss-NMR data comparison. The process can be combined with data obtained by powder diffraction. The target of this work is to test this synthetic approach for crystal structure solution.
Faculty of Chemical Technology

Pharmaceutical substances chirality identification from powder diffraction data

Hušák Michal, doc. Dr. Ing. ( hus...@vscht.cz)
Pharmaceutically interesting compounds are often not available in a form of crystals suitable for single crystal X-ray structure determination. The structure can be determined from powder - unfortunately standard experiment make chirality determination impossible. The main aim of this work will be to calibrate the crystal structure by adding an ion or cocrystallization partner with known chirality.
Faculty of Chemical Technology

Preparation of organic single crystals based on pharmaceutical materials and characterization of their properties

Čejka Jan, Ing. Ph.D. ( cej...@vscht.cz)
Král Robert, Ing. Ph.D. ( k...@fzu.cz)
Topic of this work will be focused on preparation and crystal growth of volatile and subliming organic compounds with accent on active pharmaceutical ingredients (polymorhps, solvates, salts or cocrystals) from gaseous phase and solution in order to prepare large-volume crystals thereof. The work will be focused on sublimation apparatus design and optimization of the crystal growth procedure of organic compounds from gaseous state using horizontal two section resistive furnace with separate temperature regulation. This method is based on transferring (subliming) the starting material into gaseous state in the storage part of the growth system and its subsequent crystallization (desublimation) in the dedicated coolest place of the system. Setting of suitable temperature regime in both furnace sections defines and controls the growth rate of growing crystal. An integral part of the work comprises: (i) a new crystallization container divided into storage and crystallization stages will be designed, (ii) growth conditions (temperature gradient in the furnace, temperature regimes) will be optimized, and (iii) the physical, structural and optical properties of the prepared crystals will be characterized. Second part of this work will be focused on preparation of crystals of model organic compounds grown from solution. The solvents influence on the crystallization process and final crystal quality will be evaluated. Results of characterizations performed on crystals obtained from diverse procedures as well as of used procedures will be compared.
Updated: 11.12.2019 11:36, Author: Jan Kříž

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