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Drugs and Biomaterials
Doctoral Programme,
Faculty of Chemical Technology
The Drugs and Biomaterials study programme focuses mainly on the fields of medicinal chemistry, drug analysis and the study of the structures of solid pharmaceuticals, research about and study of the properties of inorganic and polymeric materials for biomedical applications, pharmaceutical process engineering, and applied informatics for the pharmaceutical industry. CareersGraduates of this programme will be qualified for employment at universities, Czech Academy of Sciences institutes, and research and technology centres in the Czech Republic and abroad, mainly in the areas of basic and applied research of drugs and pharmaceutical forms, pharmaceutical technologies and biomaterials. Further employment opportunities for graduates are additionally to be found at R&D institutes, in analytical and control laboratories for industrial companies in these fields, and in public (governmental) administrative units, including professional R&D management positions. Programme Details
Ph.D. topics for study year 2024/25Targeted radiotherapy for the treatment of hypoxic tumors
AnnotationTreatment of hypoxic tumors is complicated due to higher radio/chemo resistance resulting in the subsequently lower clinical outcome of the treatment. We propose to explore a new concept of self-assembled polymer radiosensitizers to overcome the problem low hypoxic tumor radiosensitivity. The proposed approach is based on restoration of radiosensitivity of hypoxic cancer tissue by actively hypoxia-targeted delivery of reactive oxygen species (ROS)-precursors as well as on selective decomposition of hydrogen peroxide in hypoxic tissue influencing the HIF-1 alpha system. The proposed concept utilizes hydrophilic biocompatible polymer-based carriers with hypoxia-targeting nitroaromatics systems. The doctoral thesis will be based on synthesis, chemical and/or physicochemical characterization and study of self-assembly properties of such multi-stimuli-responsive nanoparticles with external environment; 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.
Contact supervisor
Study place:
Institute of Macromolecular Chemistry of the CAS
Surface energy heterogeneity of particulate matter
AnnotationFree surface energy is one of the important parameters in industrial applications and processes of powder and fibrous materials. Differences in surface energy affect interfacial interactions such as wetting, cohesion, or adhesion. As the wide range of uses of powders is controlled by surface reactions or interactions, the characterization of surface energies can be important information for improving surface properties (eg surface modification). General theories can only be applied to smooth, molecularly flat solid surfaces or particles. However, most interfaces for particulate matter do not have an ideally smooth surface or an ideally homogenized surface, so the work will focus on determining the heterogeneity of surface properties; heterogeneity of surface energy, and its relation to other properties of these substances.
Contact supervisor
Study place:
Department of Organic Technology, FCT, VŠCHT Praha
Kinetic, thermodynamic and structural aspects of forming solid dispersions of high-melting drugs
AnnotationHigh melting point drugs present a challenge in the formulation of amorphous solid dispersions, e.g. solid solutions with polymers, because the chemical stability of both the drug and the polymer makes it impossible to safely reach the eutectic melt formation temperature. Thus, solid dispersions are essentially formed by dissolving solid drug in the polymer melt, which creates both residence time and mixing requirements in the molten state, as well as requirements for compatibility of drugs and coformers to prevent undesired crystallization of the drug in the finished product. Therefore, this work will focus on the evaluation of compatibility of drugs and coformers by computational and experimental methods, stability of dispersions as a function of their composition and kinetics of drug dissolution in polymer melt. This main axis will be complemented by the study of the application properties of the formulations prepared with the possible support of an industrial partner. The work assumes a significant contribution to supervision from FHNW Basel.
Contact supervisor
Study place:
Department of Organic Technology, FCT, VŠCHT Praha
Modular synthesis of dendritic carriers of drugs for applications in regenerative medicine
AnnotationThe project is focused on the application of modular synthesis principles to a preparation of novel dendritic materials with properties tailored for medicinal applications, especially in the field of regenerative medicine. The first stage comprises the synthesis of a library of carbosilane building blocks (dendrons) using silicon atom as a branching point and bearing suitable peripheral functional groups (saccharide ligands, cationic groups, PEGyl chains etc.). These components will then be used for the construction of multifunctional macromolecular compounds with precisely defined dendritic structure. The application of prepared materials to the encapsulation of small molecule drugs, complexation of therapeutically active proteins and growth factors, and physically-chemical characterization of these systems will be an inherent part of the work, with emphasis on suitable pharmacokinetic and cytotoxic behavior. The work is a part of the research project supported from OP JAK fund; within this project the student will closely collaborate with external partners on the application of the prepared materials. Required education and skills • Master degree in organic chemistry, organic technology; • enthusiasm for experimental work and learning of new things; • team work ability.
Contact supervisor
Study place:
Institute of Chemical Process Fundamentals of the CAS
Molecularly imprinted polymers as a stationary phase for separation of biologically active substances of natural origin
AnnotationEssential oils and extracts from plants known for their medicinal effect contain a wide range of different substances, but not all of them have biological activity. Several procedures can be used to isolate individual biologically active compounds from plant extracts and essential oils. One of them is solid phase extraction, in which a very effective and selective separation can be achieved by choosing an optimal combination of stationary and mobile phase. Molecularly imprinted polymers (MIPs) could be a suitable alternative to conventionally used stationary phases. The advantage of MIPs is their stability, both physical and chemical. The MIP preparation process, in which cavities complementary to the desired separated molecule are formed in the polymer, is responsible for their high selectivity. It is also always necessary to optimize the preparation of the polymer itself (method, used monomers and cross-linkers, ratio of reactants, temperature, time), the process of extracting the template molecule from the polymer and, last but not least, the procedure of the solid phase extraction (conditioning of the solid phase, elution medium). Terpenic molecules will be selected for the dissertation, suitable MIPs will be prepared and the possibility of separation the selected molecules from plants will be tested.
Contact supervisor
Study place:
Department of Organic Technology, FCT, VŠCHT Praha
Computer aided design and synthesis of novel transcription factors modulators
AnnotationTranscription facrots are involved in all cellular processes. They represent a very interesting group of therapeutic targets. This project will be focused on the application of computational techniques to design new transcription factor modulators. The most promising structures will be then synthesised, purified and characterized before being biologically evaluated by our international colaborators.
Contact supervisor
Study place:
Department of Organic Chemistry, FCT, VŠCHT Praha
New concept of enhancing targeting of polymer conjugates for drug delivery to brain
AnnotationThe 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.
Contact supervisor
Study place:
Institute of Macromolecular Chemistry of the CAS
Growing Single Crystals and Structure Analysis of Multiple Component Crystals
AnnotationAPI'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.
Contact supervisor
Study place:
Department of Solid State Chemistry, FCT, VŠCHT Praha
Advanced ceramide formulations for skin barrier recovery
AnnotationCeramides are essential components of the skin barrier. Many skin diseases, e.g. atopic dermatitis or psoriasis, are connected with their pathological biosynthesis and decreased levels in the stratum corneum, the outermost skin layer. Simple topical application of ceramides shows, however, a basic shortcoming – minimum skin bioavailability. Therefore, development of advanced nanoparticulate formulations targeting ceramides right into the skin barrier seems to be a promising therapeutical procedure. This work will be performed in cooperation with an international partner. The aim will be development of nanoparticulate formulations with novel types of ceramides. Optimum process procedures, composition, and scale-up possibilities will be screened. Efficiency of the formulations will be studied in vitro in cell cultures and ex vivo in isolated skin. To charaterize the mode of action of the formulations, biophysical techniques will be applied on order to monitor interactions with the skin barrier. The best formulations will also be tested in vivo on animal models.
Contact supervisor
Study place:
Department of Organic Technology, FCT, VŠCHT Praha
Polymer colloids as specialized carriers for intranasal transport of biologically active substances
AnnotationThe project is focused on the preparation of novel polymer particles in colloidal form for therapeutic and diagnostic purposes via intranasal administration. The particles will be prepared by heterogeneous polymerisation techniques (dispersion or precipitation) and the main polymerisation reaction will be based on an aromatic substitution mechanism. Bioanalogic aromatic substances will be used as monomers. The effect of reaction conditions on the morphology and composition of particles and other physicochemical parameters determining the behaviour of particles in biological systems will be studied. Subsequently, the particles will be derivatized for their detection using preclinical imaging methods so that their biodistribution and pharmacokinetics can be monitored after intranasal administration. Biological testing of the particles will be performed at the collaborating departments of the UEM CAS and the 1st Faculty of Medicine of the Charles University. The aim of this collaboration is to describe how the composition and morphology of the particles from the new polymer types affects the mechanism of each type of intranasal delivery. The researcher will be based in the laboratories of the Institute of Macromolecular Chemistry at the BIOCEV Biotechnology Centre.
Contact supervisor
Study place:
Institute of Macromolecular Chemistry of the CAS
Polymer carriers for the treatment of stroke
AnnotationTreatment of stroke, which is one of the deadliest disorders, has improved tremendously in recent years. Pharmacological treatment, i.e., intravenous thrombolysis, will still remain a keystone of acute stroke treatment. Unfortunately, there is still a limited amount of suitable and effective thrombolytics; thus, there is a potential for improvement, especially in using polymer carriers. Polymer carriers are non-toxic, non-immunogenic, and biocompatible polymer materials enabling targeting and controlled release of biologically active compounds in the treated tissue and thus minimizing side-effects of carried active compounds. The doctoral project theme will consist of synthesizing and studying the properties of tailor-made polymer carriers of thrombolytics. The topic is suitable for graduates of chemistry, eventually pharmacy. The student will learn new skills in the synthesis and methods of characterization and can participate in biological characterization. We offer exciting and varied work in a well-established team of Biomedical polymers, affording hi-tech equipment and material background.
Contact supervisor
Study place:
Institute of Macromolecular Chemistry of the CAS
Modeling of drug release from the solid dispersions by diffusion erosion models
AnnotationThis 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.
Contact supervisor
Study place:
Department of Organic Technology, FCT, VŠCHT Praha
Synthesis of inhibitors of the Arp2/3 complex
AnnotationMigrastics represent a new approach to cancer treatment. Their aim is to prevent metastasis of cancer cells. One suitable target for the development of migrastatics is the Arp2/3 protein complex, which initiates actin polymerization at microfilament branching sites. In this work, inhibitors of the Arp2/3 complex will be prepared based on virtual screening data. The relationship between their structure and activity will be studied and their pharmacological properties will be further optimized.
Contact supervisor
Study place:
Department of Organic Chemistry, FCT, VŠCHT Praha
Preparation of organic single crystals based on pharmaceutical materials and characterization of their properties
AnnotationTopic 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.
Contact supervisor
Study place:
Department of Solid State Chemistry, FCT, VŠCHT Praha
Radioactive and fluorescent labeling of polymers and nanoparticles for medicine and preclinical testing
AnnotationThis doctoral thesis focuses on the development and optimization of labeling techniques for polymers and nanoparticles in the field of medicine. The labeling allows for tracking and provides valuable information for therapy and next biological testing.
Contact supervisor
Study place:
Institute of Macromolecular Chemistry of the CAS
Self-cleaning anti-biofilm polymer surfaces
AnnotationThe 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.
Contact supervisor
Study place:
Institute of Macromolecular Chemistry of the CAS
Monitoring and prediction of tablet disintegration behavior using texture analysis
AnnotationThe disintegration kinetics of tablets is a determining step for their overall dissolution behavior, as it determines the size and specific surface area of the fragments produced during their disintegration. This kinetics depends on the rate of penetration of the disintegration medium into the tablet microstructure, both into the pores and swelling components of the tablet, and the ability of the internal dissolution and swelling processes to disrupt the tablet cohesion. The aim of this work is to study the kinetics of water absorption into the tablet as a function of its composition and microstructure by means of textural analysis and microscopic measurements, to study the resistance of the tablet to erosive effects as a function of the amount of absorbed liquid as well as the size of the fragments formed as a result of these processes. The knowledge obtained should then be used to develop a fully or partially predictive model capable of predicting disintegration behavior based on the microstructure of the tablet and the physical properties of its components.
Contact supervisor
Study place:
Department of Organic Technology, FCT, VŠCHT Praha
Stability of interactive mixtures and their use for drug delivery
AnnotationInteractive mixtures are self-organizing systems of host-guest particles that form as a result of preferential inter-surface interactions. In addition to their well-known use in powder inhalers, they may find applications in other areas of drug delivery, e.g. to increase the dissolution rate of poorly soluble drugs. The aim of this work will be to study the interparticle inter-surface interactions using surface energy measurements, atomic force microscopy, and centrifugation methods, to define the stability conditions of the interactive aggregates based on the properties measured using those methods, and to find methods of designing a stable interactive mixture for a specific drug.
Contact supervisor
Study place:
Department of Organic Technology, FCT, VŠCHT Praha
Study of the stability of APIs in mixtures with respect to their processing and composition
AnnotationDrug stability is one of the fundamental qualitative attributes that must be evaluated in the context of drug research and development. Without sufficient information on the stability of the medicinal product, it is not possible to obtain a marketing authorisation and to place the product on the market. Significant effort is invested at the beginning of development to select the optimal API form for further downstream development steps. Understanding the stability of the selected API formulation is important for appropriate choice of manufacturing processes and quality assurance of the finished products. The scope of the work will be to study both the chemical and physical stability of different APIs in terms of formulation composition and type of mixture preparation or process treatment.
Contact supervisor
Study place:
Department of Organic Technology, FCT, VŠCHT Praha
Stimuli-responsive supramolecular polymer systems for biomedical applications
AnnotationSelf-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.
Contact supervisor
Study place:
Institute of Macromolecular Chemistry of the CAS
Synthesis of novel protein degraders as antiviral agents
AnnotationProtein degraders, as PROTACs and molecular glues, have emerged as a very powerful strategy in the development of novel therapeutic agents. This project will explore the application of this approach in the design of novel, innovative, antiviral agents.
Contact supervisor
Study place:
Department of Organic Chemistry, FCT, VŠCHT Praha
The use of surface energy as a tool for the formulation applications
AnnotationPharmaceutical products are sophisticated mixtures of numerous compounds that can be liquids or solids. However, there is still the problem how to select them efficiently without costly and time-consuming tests that are associated with the complexity of the drug development. Surface energy could be used as powerful prediction tool to perform such selections. The aim of this work is to provide a new perspective on the prediction of component compatibility (API and excipient) for formulation design for the production of solid dosage forms based on the surface properties of their components.
Contact supervisor
Study place:
Department of Organic Technology, FCT, VŠCHT Praha
Development and optimization of continuous wet granulation process
AnnotationWet granulation process is commonly used to increase of drug particle size, improve of drug particle flowability or its physicochemical properties. Commonly, the wet granulation process is done in a batch mode using high shear granulators. However, during the process scale up there is often difference in the final granule properties including size, composition, homogeneity, porosity etc. All these parameters have impact on the rate of drug product disintegration and drug dissolution. Therefore, the main goal of this work is to develop and optimize process of wet granulation using continuous operation mode via extrusion process. Process parameters will cover ratio of drug particle to binder, binder type, size and surface properties of drug particles, mixing intensity, applied shear rate and residence time in the extruder. As an alternative to water-based binders, we will investigate also possibility to use oil-based binders or water emulsions, targeting higher bioavailability. Obtained granules will be characterized by a combination of various methods including API crystal form stability (XRD), size characterization (optical and electron microscopy, light scattering), porosity measurement (BET, Hg porosimetry, tomography), composition (Raman mapping, FTIR, NIR spectroscopy), powder rheology and granule disintegration kinetic. Collected results will be compared with those measured for granules obtained from batch process, targeting development of criteria for process transfer from small-scale batch process to continuous operation. In the last stage we will investigate in-vivo testing of binder type on the drug bioavailability.
Contact supervisor
Study place:
Department of Chemical Engineering, FCE, VŠCHT Praha
Development of membrane model systems to predict permeability of drugs
AnnotationThe basic step in the absorption of drugs into the body is their permeation across the cell membrane. However, it is difficult to study this phenomenon in complex organ systems. The aim of this thesis will be to establish artificial lipid membrane models that will be used for in vitro study of drug permeation. Different types of lipid systems mimicking the structure of biological membranes of selected tissues (intestinal lumen, sublingual, dermal tissue, etc.) will be developed. Membranes will be characterized in detail at the molecular level using biophysical methods (SAXS, FTIR, Raman spectroscopy, AFM and others). Furthermore, permeation kinetics will be studied on the membranes for a series of active compounds with different physicochemical properties. The data obtained will be correlated with more complex in vitro cellular models and ex vivo models. Correlation with in silico models will also be applied in the collaboration with oth. The main output of the project will be valid model systems that have the potential to predict the permeation behaviour of drugs in more complex biological environments.
Contact supervisor
Study place:
Department of Organic Technology, FCT, VŠCHT Praha
Development of nanoparticulate formulations targeting skin cancer
AnnotationSkin tumours are identified with increasing incidence. Currently, topical treatment is substantially limited by low bioavailability of anticancer drugs. The aim of this work is development of nanoparticulate systems (e.g. liposomes, lipid and polymer nanoparticles) and monitoring their potential to target drugs into skin tumours. Nanocarriers loaded with active compounds for cancerous and precancerous stages will be prepared and characterised. Their ability to transport the drug across the skin barrier and interactions with cancer tissue will be studied in vitro and ex vivo. Processing of the most promising systems will be optimized for in vivo experiments in mice cancer models where the drug/nanoparticle transport and release kinetics in the tumour will be monitored. The results will contribute to fundamental understanding of relationships between the nanoformulation, its properties and biological effects in cancer tissue.
Contact supervisor
Study place:
Department of Organic Technology, FCT, VŠCHT Praha
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Updated: 20.1.2022 16:26, Author: Jan Kříž