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PhD topics for academic year 2021/2022

Department of Organic Chemistry

Synthesis and Production of Drugs - Drugs and Biomaterials

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.

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 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

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

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)
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)
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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