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Drugs and Biomaterials

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.

Careers

Graduates 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

Study Language English
Standard study length 4 years
Form of study full-time , combined
Guarantor prof. Ing. Radek Cibulka, Ph.D.
Place of study Praha
Capacity 30 students
Programme code (national) 2801V024
Programme Code (internal) LB_AJ
Number of Ph.D. topics 16

Ph.D. topics for study year 2022/23

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 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, UCT Prague

Bioactive coatings promoting spontaneous endothelialization of vascular vessel grafts

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

Annotation


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.
Contact supervisor Study place: Institute of Macromolecular Chemistry CAS

Biodegradable polymer systems for medical applications

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

Annotation


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).
Contact supervisor Study place: Institute of Macromolecular Chemistry CAS

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

Functionalized polymer drug carriers

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

Annotation


Polymer drug 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 drugs. The doctoral project theme will consist in synthesis and study of properties of tailor-made hydrophilic or amphiphilic polymers efficient as sole carriers of drugs, namely cancerostatics, or thrombolytics, as well as materials for surface modification of other drug delivery systems, e.g. nanoparticles, liposomes, to increase their biocompatibility. The theme 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 in internal or international cooperating laboratories. We offer interesting 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

Design and optimization of unit operations for continuous manufacturing of solid dosage forms

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

Annotation


The continuous manufacturing of solid dosage forms is a very progressive way to increase the production efficiency of products manufactured in a large number of batches. Compared to the traditional batch-oriented approach, it requires new approaches for quality control, prefers different types of unit operations and consequently, there are different preferences in the formulation of products intended for this production method. The aim of this work is to provide a new perspective on the formulation and design of technological procedures for the production of tablets and other solid dosage forms in the light of the focus on continuous manufacturing. In particular, the work will focus on continuous mixing processes, segregation of the mixture in a continuous line, roll compaction and its setup from the perspective of tablet compression.
Contact supervisor Study place: Department of Organic Technology, UCT Prague

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, UCT Prague

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, UCT Prague

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, UCT Prague

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

Granting Departments: Department of Polymers
Institute of Macromolecular Chemistry CAS
Supervisor: Mgr. Eliézer Jäger, Ph.D.

Annotation


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.
Contact supervisor Study place: Institute of Macromolecular Chemistry CAS

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 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

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, UCT Prague

Polymer-based drug delivery vectors targeting stemness and metabolism of glioblastoma cells

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

Annotation


Topic of the thesis will be focused on the development of targeted polymeric drugs for treatment of glioblastoma (GBM), the most common brain cancer. Current GBM treatment is resection of GBM with the risk of damaging healthy tissue, followed by radio- and chemotherapy. Another treatment is not available, treated patients survive 12 months longer than untreated. The aim of the work is to design structures, synthesis, physico-chemical characterization and verification of the biological activity of nanodrug designed for targeted multimodal GBM therapy. Nanodrug should: effectively cross the blood-brain barrier (BBB); specifically target to tumor and affect the metabolism of cancer cells. Advantage of this approach is that targeting peptide and BBB-penetrating peptides are bound to one polymer carrier bearing drug, which will be in its inactive form during transport and released after reaching tumor. Student will participate in synthesis of monomers, polymeric carriers and selected peptides on solid phase, study of binding of peptides and drugs to polymer precursor, physicochemical characterization of all products and in vitro study of biological properties of prepared conjugates on different cell lines and in cooperation with IEM CAS testing crossing of BBB on a perfusion model.
Contact supervisor Study place: Institute of Macromolecular Chemistry CAS

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, UCT Prague

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
Updated: 20.1.2022 16:26, Author: Jan Kříž

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