Studentská vědecká konference

The targeted delivery of specific Active pharmaceutical ingredients (APIs) to the required site of effect inside human body is complicated and recently often studied problem, because when API is not specifically targeted various adversary effects can occur, such as reaction of API with surrounding environment, poor solubility in body fluids, immune response, etc. Liposomes can be used as vessels for such targeted delivery for some APIs like doxorubicin, daunorubicin or cytarabine. However, they are not suitable for all APIs due to complications with encapsulation of the APIs into the liposomes. One of the possible solutions for this problem is to first adsorb the API into a porous particle and then encapsulate the particle itself into the liposome. The formed nanocomposites are called protocells. The aim of this work is to prepare silica nanoparticles, adsorb a model set of APIs into them and encapsulate the particles into liposomes to form protocells. Further aim of this work is to prove that using this way it is possible to encapsulate APIs which are not possible to be encapsulated into simple liposomes.  

Majority of newly synthesized drugs is characterized by poor water solubility, which can be improved either by amorphization or by loading into a carrier, for example mesoporous silica particle. This work focuses on preparation of so-called protocells – mesoporous silica nanoparticles encapsulated in liposomes, where liposomes act as gatekeepers and prevent undesired drug leakage. Such formulations allow us to deliver the drug into specific sites, for example tumours (passive targeting via EPR effect, or antibody-mediated active targeting). This work contains synthesis of the silica nanoparticles (180 nm) and its optimization, subsequent loading of the model substance, preparation of the protocells and evaluation of the loading capacity and release kinetics.  

Hydrogel microparticles are hydrophilic microparticles with the ability to incorporate various functional components such as liposomes, nanoparticles or enzymes. Microfluidics allows us to prepare monodisperse microparticles in sizes comparable to those of blood cells, i.e. 5 to 10 µm, which makes them suitable for targeted drug delivery. These microparticles can be used as miniature chemical or biochemical reactors in order to store, deliver, chemically process and locally release pharmaceutically active substances that are highly reactive or unstable, and therefore cannot be delivered in standard dosage forms. Targeted drug delivery improves efficiency and decreases side-effects of a drug by avoiding interactions with healthy tissue. The goal of this project is to synthesize hydrogel microparticles which are able to deliver and in response to an external radiofrequency signal release active matter, e.g. allicin, a highly potent natural antibiotic compound found in garlic. In the current stage, alginate microparticles containing iron oxide nanoparticles and liposomes with encapsulated carboxyfluorescein dye were successfully prepared in a microfluidic chip and analysed by confocal microscopy.

Hydrogels are cross-linked materials capable of absorbing large amounts of water without dissolving. They are used in broad spectrum of bioapplications such as drug delivery and tissue engineering. For these uses specific shapes of particles are required. Thus, the focus of the scientists has shifted to lithographic synthesis of such hydrogels. Most of lithographic methods use light to determine the shape of synthesized objects, therefore, synthetic photocrosslinkable polymers are used as substrates. However, biopolymers offer much better biocompability over synthetic polymers, which is crucial in bioapplications. Biopolymers can be crosslinked using various methods, but light is not one of them, which prevents their lithographic processing. In this work, we utilized synthetic polymer as sacrificial template to generate biopolymer particles of desired shape. We successfully prepared mixture of biopolymer (chitosan) and template polymer (methacrylated dextran). Synthetic polymer was crosslinked via stop-flow lithography to gain desired shape and then we used genipin to crosslink entrapped biopolymer. Synthetic polymer was then hydrolysed under basic conditions yielding solely biopolymer particles.    

Urea-Urease system is promising system for the bio regeneration of concrete material. The cracks in concrete can be filled with solution of powdered chalk (CaCO₃) dissolved in lactic acid creating a Ca²⁺ solution and then other solution of urea and urease should be added. The urease solution hydrolyse urea producing ammonia and bicarbonate ions that can precipitate and produce calcium carbonate [1]. Urea-urease system has bell shaped activity curve from pH 3 to 11 showing maximum at pH 7. If the higher pH is caused by ammonia, it creates negative feedback [2], which may lead into pH dynamic regimes. That can be used in breathing microgel reactors [3]. In this study we used CSTR (2.86ml) with three inflows, specifically: urea (0.0015M, F₀~0.08ml/min), urease (5U/ml, F₀~0.33ml/min) and sulphuric acid solutions (pH=<2.624; 4.81>, F₀~0.08ml/min) under 25°C. Different concentrations of acid were used to find dynamic behaviour. pH was measured using pH probe theta 113vfr and pH meter HI 5222-02.   [1]          Phua, Y.J. and A. Røyne, Construction and Building Materials, 2018, 167, 657-668. [2]          Hoare, J. P. and Laidler K. J., J. Am. Chem. Soc., 1950, 72 (6), 2487–2489 . [3]          Che, H., S. Cao, and J.C.M. van Hest,. J. Am. Chem. Soc., 2018, 140(16),5356-5359.

In recent years, nanoparticles have essential role in various areas such as biomedical, environmental or pharmaceutical applications due to their chemical and physical properties. In all these applications, ensuring control over the particle size and shape has high importance due to their size and shape dependent attributes. The most traditional nanoparticle synthesis method is the batch process due to its fast and easy reaction setup. However, abundant types of nanoparticles are very sensitive to the reaction parameters which directly affect the final particle size and shape. Thus, the process is hardly reproducible. In this work, we present silver nanoparticle synthesis using a droplet generation in microfluidic device. Microfluidic setup offers higher control over the reaction process by easy control and flexible settings of the system parameters (e.g. mixing and flow rates of the reagents) than batch process. The size and morphology of the final nanoparticles are analyzed and compared to batch process.

One of the ways how to administer a poorly water soluble drug into human body is a long-acting intramuscular suspension. Such formulation offers many advantages when compared with conventional formulations of the same compounds. These advantages include: predictable drug-release profile over a defined time period, decreased side effects, improved systemic availability by avoidance of first-pass effect, etc. The goal of this work is to design an in vitro dissolution method for a particular depot suspension of an inactive medication. After the administration the suspension remains inside the muscle in a form of depot. Solid particles slowly dissolve into tissue fluid and the prodrug is enzymatically metabolized to the active drug. Particle size and surface area are limiting step for dissolution kinetic of this formulation. By mimicking of in vivo conditions in in vitro environment we are enabled to investigate dissolution profile of a depot formulation before in vivo studies. This method would be beneficial in a generic drug development or the enhancement of the formulation in a personalized medicine. For this purpose the development of HPLC method, parametric study of the suspension nano-milling and the sample preparation methodology were carried out.  

FDM (fused deposition modeling) 3D printing is an innovative, fast-growing method of rapid prototyping where a solid object is formed by the printer according to a supplied 3D drawing. Its application can be found throughout many areas of industry, science or even medicine and pharmacy. Since recently, it is considered to be a possible alternative method for drug dosage form manufacturing. Current manufacturing methods operate with very large batches and usually the API (active pharmaceutical ingredient) dosage and shape of the tablets are set for the whole process. A popular new approach to medication and care (personalized medicine), where the whole treatment is tailored to a specific patient needs, requires new methods of drug dosage form manufacturing where only small batches will be produced, dosage of the API can easily be adjusted and dissolution kinetics of the API can be controlled. Goal of this work is to produce two types of biodegradable filaments (feed for 3D printer) with each of them containing one model API. Models of tablets will be designed to yield various dissolution profiles of each API. This will be achieved by changing inner porosity and outer surface area of tablets. Dissolution kinetics will be then measured by dissolution tests.

Taylor reactor (TR) is a batch reactor made from two concentric rotating cylinders separated by fluid (Fig. 1a). In real applications modification with steady external cylinder called Taylor-Couette reactor (TCR) is used.  TCRs are in general employed for homogenous mixing of highly viscous mixtures such as substrates for enzymatic catalyzes, also for preparation of submicron particles (lower viscosity) or reactions, but their feasibility for microparticle synthesis still needs to be investigated. This work is based on findings previously reported in my bachelor thesis, where TCR for the preparation of silica particles was used (Fig. 1b). The goal of this work is an improvement of batch preparation of microparticles by means of continuous TCR and use of narrower shear rate distribution provided by TCR to decrease a polydispersity of produced particles. In pursuit of achieving this goal TCR was redesigned with the lower ratio between the height of reactor and gap between cylinders. Results of this work may contribute to continuous production particles with lower polydispersity compared to common batch-wise synthesis. Additionally, the mathematic model will be prepared to bring insight into nontrivial flow regimes typical for TCR and particle synthesis.  

The increasingly stringent automotive emission regulations enforce the use of particulate filters to effectively control the particulate emissions from both diesel and gasoline engines. Due to the cost and size limitations of the exhaust gas after-treatment system, it is favorable to combine the particulate filter with a catalytic reactor for conversion of gaseous pollutants. The properties of the resulting catalytic filter are highly dependent on the quality of the catalytic coating. In order to accelerate the design process of catalytic filters, it is necessary to understand the relation between the device microstructure, e.g. the pore structure and coating distribution, and the full device performance (pressure drop, conversion and filtration efficiency). This study represents one part of a reliable multi-scale CFD model development for catalytic filters. A new boundary condition mapping was developed to transfer the flow data from a macro-scale model of the entire filter channel to a micro-scale simulation of the porous wall. In this way, a more realistic prediction of flow field in the wall microstructure was achieved, which provided improved estimates of the device filtration efficiency depending on the substrate and catalytic coating properties.