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Drugs and Biomaterials

Drugs and Biomaterials

Doctoral Programme, Faculty of Chemical Technology

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Careers

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Programme Details

Study Language Czech
Standard study length 4 years
Form of study combined , full-time
Guarantor prof. Ing. Radek Cibulka, Ph.D.
Place of study Praha
Capacity 30 students
Programme code (national) P0531D130072
Programme Code (internal) D105
Number of Ph.D. topics 37

Ph.D. topics for study year 2024/25

Inorganic carriers of active pharmaceutical ingredients

Granting Departments: Department of Solid State Chemistry
Supervisor: prof. Ing. František Kovanda, CSc.

Annotation


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 the interlayer, stability of intercalated drugs, and their back release in simulated body fluids will be studied.
Contact supervisor Study place: Department of Solid State Chemistry, FCT, VŠCHT Praha

Automation of active organic compounds crystal structure verification based on comparison with DFT calculations.

Granting Departments: Department of Solid State Chemistry
Supervisor: doc. Dr. Ing. Michal Hušák

Annotation


The topic of this work is verification of experimental crystal structures base don comparison with DFT calculations results. The main goal is to optimize the DFT calculations parameters for given task and to develop software for the task automatic processing.
Contact supervisor Study place: Department of Solid State Chemistry, FCT, VŠCHT Praha

Targeted radiotherapy for the treatment of hypoxic tumors

Granting Departments: Department of Polymers
Institute of Macromolecular Chemistry CAS
Supervisor: doc. Mgr. Martin Hrubý, Ph.D., DSc.

Annotation


Treatment 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 CAS

Design, synthesis and full technology transfer of ion-exchange type stationary phases for HPLC: from primary research to pharmaceutical practice

Granting Departments: Department of Organic Chemistry
Supervisor: prof. Ing. Michal Kohout, Ph.D.

Annotation


High performance liquid chromatography (HPLC) is the world’s leading method for final purification of most active pharmaceutical substances. Despite undoubtful progress in numerous areas of this field in recent years, resolution of polar ionised and ionisable analytes still represents a very challenging task to solve. Moreover, most advancements achieved are of purely academic nature and are not transferred into any actual technology used in practice. The present Ph.D. project covers the full scope of research and development of a new portfolio of brush-type stationary phases bearing ion-exchange selectors intended for both chiral and achiral separations of ionised and ionisable compounds. The candidate is expected to synthesise a new library of cation exchangers (CX), anion exchangers (AX) and zwitterion ion exchangers (ZW) derived from natural precursors (e.g., cinchona alkaloids, amino acids, etc.). The prepared selectors will be immobilised to silica gel solid support and tested as separation media for various sets of analytes (e.g., amino acids, organic acids, basic drugs, short peptides, etc.). In collaboration with our laboratory spinoff - Galochrom s.r.o., the synthesis of the stationary phases with the best separation performance will be scaled-up and marketed as a part of the new generation of Galochrom’s product portfolio. Therefore, a direct industrial impact, particularly on pharmaceutical industry, of the Ph.D. project is expected.
Contact supervisor Study place: Department of Organic Chemistry, FCT, VŠCHT Praha

Surface energy heterogeneity of particulate matter

Granting Departments: Department of Organic Technology
Supervisor: Ing. Jan Patera, Ph.D.

Annotation


Free 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

Smart antimicrobial materials

Granting Departments: Department of Solid State Engineering
Supervisor: prof. Ing. Václav Švorčík, DrSc.

Annotation


V současnosti kolem 80 % bakteriálních onemocnění pochází od biofilmů. Biofilm představuje bakteriální kolonii, která je ukotvená na povrchu a natočena specifickou “zdí”, díky čemuž je schopna se bránit běžné antimikrobiální léčbě. Další nebezpečné jevy probíhající v biofilmu souvisí s bakteriálním quorum-efektem a velkým rizikem vývoje rezistence vůči antibiotikům. Proto prevence tvorby a ničení biofilmů představuje jednu z klíčových otázek v oblasti materiálů pro medicínu. Tradiční způsoby jako je inkorporace antimikrobiálních látek nejenže často selhávají, ale mohou vést i k řadě nežádoucích efektů, jako je nárůst výše zmíněné resistivity vůči antibiotikům nebo dalším antimikrobiálním látkám. V této práci bude realizován nový způsob obrany medicinských povrchů proti biofilmům – použití povlaků na bázi smart materiálů. Díky svému složení tyto povrchy zaručí dvojitou obranu – prevence před bakteriální kolonizaci a současně jsou schopny uvolňovat antimikrobiální sloučeniny.
Contact supervisor Study place: Department of Solid State Engineering, FCT, VŠCHT Praha

Pharmaceutical substances chirality identification from powder diffraction data

Granting Departments: Department of Solid State Chemistry
Supervisor: doc. Dr. Ing. Michal Hušák

Annotation


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.
Contact supervisor Study place: Department of Solid State Chemistry, FCT, VŠCHT Praha

Inhalational drug nanocrystals for systemic delivery

Granting Departments: Department of Chemical Engineering
Supervisor: Ing. Denisa Lizoňová, Ph.D.

Annotation


This PhD project will focus on the design, preparation, and optimization of an aerosol drug nanocrystal fabrication process as a promising strategy for systemic delivery of poorly soluble low molecular weight drugs via the inhalation route. With a primary focus on nanocrystal preparation and aerosolization, the research aims to develop efficient techniques for the production of inhalable drug nanocrystals. The study will investigate different methods of nanocrystal preparation (wet milling, continuous precipitation) and evaluate their effectiveness in producing stable monodisperse nanocrystals that allow for better drug dissolution and thus higher bioavailability. In addition, the research will focus on the development and validation of aerosolization devices to ensure optimal drug delivery of nanocrystals. Through this research, the thesis aims to contribute to the development of non-invasive drug delivery methods, which will ultimately facilitate the introduction of new therapeutic agents into clinical practice. The student will learn techniques for the preparation and characterization of nanocrystals, the preparation and characterization of aerosols, and other methods necessary for the research project. In addition, the student will have the opportunity to collaborate within a multidisciplinary research team and present and publish their research.
Contact supervisor Study place: Department of Chemical Engineering, FCE, VŠCHT Praha

Cell interaction with periodic nano- and microstructured surfaces

Granting Departments: Department of Solid State Engineering
Supervisor: prof. Ing. Petr Slepička, Ph.D.

Annotation


Contact supervisor Study place: Department of Solid State Engineering, FCT, VŠCHT Praha

Kinetic, thermodynamic and structural aspects of forming solid dispersions of high-melting drugs

Granting Departments: Department of Organic Technology
Supervisor: prof. Ing. Petr Zámostný, Ph.D.

Annotation


High 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

Granting Departments: Department of Organic Chemistry
Institute of Chemical Process Fundamentals of the CAS, v.v.i.
Supervisor: Ing. Tomáš Strašák, Ph.D.

Annotation


The 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, v.v.i.

Molecularly imprinted polymers as a stationary phase for separation of biologically active substances of natural origin

Granting Departments: Department of Organic Technology
Supervisor: doc. Ing. Eliška Vyskočilová, Ph.D.

Annotation


Essential 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

Granting Departments: Department of Organic Chemistry
Supervisor: Ing. Petra Cuřínová, Ph.D.

Annotation


Transcription 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

Granting Departments: Department of Polymers
Institute of Macromolecular Chemistry CAS
Supervisor: Ing. Jiří Pánek, Ph.D.

Annotation


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.
Contact supervisor Study place: Institute of Macromolecular Chemistry CAS

Growing Single Crystals and Structure Analysis of Multiple Component Crystals

Granting Departments: Department of Solid State Chemistry
Supervisor: Ing. Jan Čejka, Ph.D.

Annotation


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.
Contact supervisor Study place: Department of Solid State Chemistry, FCT, VŠCHT Praha

Advanced bactericidal coatings with long-lasting effect

Granting Departments: Department of Solid State Engineering
Supervisor: prof. Ing. Jakub Siegel, Ph.D.

Annotation


Scientific task 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 UCT Prague and Institute of Physiology CAS.
Contact supervisor Study place: Department of Solid State Engineering, FCT, VŠCHT Praha

Advanced ceramide formulations for skin barrier recovery

Granting Departments: Department of Organic Technology
Supervisor: doc. Mgr. Jarmila Zbytovská, Dr. rer. nat.

Annotation


Ceramides 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

Granting Departments: Department of Polymers
Institute of Macromolecular Chemistry CAS
Supervisor: Ing. Michal Babič, Ph.D.

Annotation


The 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 CAS

Polymer carriers for the treatment of stroke

Granting Departments: Department of Polymers
Institute of Macromolecular Chemistry CAS
Supervisor: RNDr. Petr Chytil, Ph.D.

Annotation


Treatment 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 CAS

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

Granting Departments: Department of Organic Technology
Supervisor: prof. Ing. Petr Zámostný, Ph.D.

Annotation


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.
Contact supervisor Study place: Department of Organic Technology, FCT, VŠCHT Praha

Synthesis of inhibitors of the Arp2/3 complex

Granting Departments: Department of Organic Chemistry
Supervisor: Mgr. et Mgr. Pavla Perlíková, Ph.D.

Annotation


Migrastics 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

Synthesis of inhibitors of transcription factors involved in metabolic diseases

Granting Departments: Department of Organic Chemistry
Supervisor: Mgr. et Mgr. Pavla Perlíková, Ph.D.

Annotation


Transcription factors play an important role in the regulation of gene expression. Deregulation of key protein synthesis leads to a variety of metabolic diseases. The aim of this work is to use rational drug design to prepare suitable inhibitors of selected transcription factors and to further investigate the structure-activity relationship.
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

Granting Departments: Department of Solid State Chemistry
Supervisor: Ing. Jan Čejka, Ph.D.

Annotation


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.
Contact supervisor Study place: Department of Solid State Chemistry, FCT, VŠCHT Praha

Preparation of substrates for tissue engineering of blood vessels and skin.

Granting Departments: Department of Solid State Engineering
Supervisor: Ing. Nikola Slepičková Kasálková, Ph.D.

Annotation


This work aims to expand the boundaries of regenerative medicine, a multidisciplinary field that deals with restoring or replacing damaged tissues and organs. The main task will be developing and evaluating new substrates for tissue engineering focused on the regeneration of tissue that cannot be treated by standard methods or tissue with a limited ability to regenerate. It will mainly be about substrates for the replacement of small vessels and the treatment of chronic wounds.
Contact supervisor Study place: Department of Solid State Engineering, FCT, VŠCHT Praha

Radioactive and fluorescent labeling of polymers and nanoparticles for medicine and preclinical testing

Granting Departments: Department of Polymers
Institute of Macromolecular Chemistry CAS
Supervisor: RNDr. Jan Kučka, Ph.D.

Annotation


This 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 CAS

Reconstruction of crystal structures based on known intermolecular interactions

Granting Departments: Department of Solid State Chemistry
Central Laboratories
Supervisor: Ing. Jan Sýkora, Ph.D.

Annotation


The main aim of the work is to develop a software tool for creating of possible 3D structures based on empirically determined and/or assumed interactions between molecules in a microcrystalline, polycrystalline or amorphous material. Such a software will served for identification of different solid-phase forms of a given pharmaceutical substance.
Contact supervisor Study place: Central Laboratories

Self-cleaning anti-biofilm polymer surfaces

Granting Departments: Department of Polymers
Institute of Macromolecular Chemistry CAS
Supervisor: doc. Mgr. Martin Hrubý, Ph.D., DSc.

Annotation


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.
Contact supervisor Study place: Institute of Macromolecular Chemistry CAS

Monitoring and prediction of tablet disintegration behavior using texture analysis

Granting Departments: Department of Organic Technology
Supervisor: prof. Ing. Petr Zámostný, Ph.D.

Annotation


The 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

Granting Departments: Department of Organic Technology
Supervisor: prof. Ing. Petr Zámostný, Ph.D.

Annotation


Interactive 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

Granting Departments: Department of Organic Technology
Supervisor: Ing. Jan Patera, Ph.D.

Annotation


Drug 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

Granting Departments: Department of Polymers
Institute of Macromolecular Chemistry CAS
Supervisor: doc. Mgr. Martin Hrubý, Ph.D., DSc.

Annotation


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.
Contact supervisor Study place: Institute of Macromolecular Chemistry CAS

Synthesis of novel protein degraders as antiviral agents

Granting Departments: Department of Organic Chemistry
Supervisor: prof. Andrea Brancale, Ph.D.

Annotation


Protein 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

Granting Departments: Department of Organic Technology
Supervisor: Ing. Tereza Školáková, Ph.D.

Annotation


Pharmaceutical 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 utilization of advanced in vitro models for inhalational drug delivery

Granting Departments: Department of Chemical Engineering
Supervisor: Ing. Denisa Lizoňová, Ph.D.

Annotation


The main objective of this Ph.D. project is to develop highly organized cell culture models of the human respiratory tract, which can be used for studying systemic drug delivery through inhalational route. Specific Objectives: 1. Development of an in vitro alveolar air-liquid interface model using alveolar cell lines to study drug absorption and particle translocation through the alveolar barrier. 2. Establishment of an in vitro tracheobronchial (TB) model using TB epithelial and goblet cell lines to investigate drug nanocrystal permeation and retention in the mucus barriers. 3. Characterization of drug absorption, translocation, and mucus penetration properties of aerosolized drug nanocrystals using the developed in vitro lung models. 4. Optimization of nanocrystal size and surface chemistry (in collaboration with other research team members) to enhance drug absorption, minimize macrophage uptake, and improve mucus penetration for efficient systemic delivery. Apart from the research itself, the student will have the opportunity to collaborate within a multidisciplinary research team and present and publish their research
Contact supervisor Study place: Department of Chemical Engineering, FCE, VŠCHT Praha

Development of membrane model systems to predict permeability of drugs

Granting Departments: Department of Organic Technology
Supervisor: doc. Mgr. Jarmila Zbytovská, Dr. rer. nat.

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The 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 methodology for analysis of trace amount of pharmacologic products using advanced spectroscopic techniques

Granting Departments: Department of Physical Chemistry
Supervisor: Ing. Marcela Dendisová, Ph.D.

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V přírodě, a hlavně v odpadních vodách, se vyskytuje čím dál větší množství residuí farmakologických přípravků, jako jsou hormonální přípravky, antibiotika, výživové doplňky a jiné. Jejich rostoucí množství má neblahý vliv na životní prostředí a je tudíž zapotřebí najít spolehlivý nástroj pro jejich detekci a analýzu. K tomu mohou sloužit metody povrchem zesílené vibrační spektroskopie, které jsou využívány pro detekci látek o nízkých koncentracích. Před využitím těchto metod v praxi je zapotřebí studovat adsorpční procesy daných farmakologických látek s využitím technik povrchem-zesílené vibrační spektroskopie, zahrnující Ramanův rozptyl a infračervenou absorpci. Dalším krokem je využití technik blízkého pole založených na mikroskopii skenující sondou. Tyto techniky umožňují sledovat optickou odezvu v závislosti na experimentálních podmínkách (materiál substrátu, energie budícího záření, morfologie povrchu, …) a nalézt optimální podmínky pro jejich detekci.
Contact supervisor Study place: Department of Physical Chemistry, FCE, VŠCHT Praha

Development of nanoparticulate formulations targeting skin cancer

Granting Departments: Department of Organic Technology
Supervisor: doc. Mgr. Jarmila Zbytovská, Dr. rer. nat.

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Skin 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
Updated: 25.3.2022 18:16, Author: Jan Kříž

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