Nanofibers in Mucosal Drug and Vaccine Delivery

Successful mucosal administration and delivery of drugs still pose a great challenge. However, the possibility to deliver not only small drug molecules but also macromolecular drugs and nanoparticles via mucosal surfaces represents a great opportunity. Rapid onset of drug action, avoidance of first-pass metabolism, and high immunocompetence of mucosa are some of the important features for mucosal drug and vaccine delivery. The use of mucoadhesive drug delivery systems, systems with fast dissolving properties, and nanomaterials with mucus penetration properties are examples of successful strategies to achieve effective mucosal drug and vaccine delivery. Non-keratinized mucosa of the oral cavity, the nasal and vaginal mucosa represent favorable sites of drug administration. Polymer nanofibers have attracted much attention because of remarkable characteristics such as a large surface area to volume ratio and high porosity. Nanofibers have been extensively used for different biomedical applications including wound dressing, tissue engineering, and drug delivery. Among their fabrication methods, the introduction of electrospinning technique was an important step toward achieving the goal of large scale industrial production of nanofiber-based drug delivery systems used in mucosal applications. This chapter provides an overview on all aspects of mucosal drug and vaccine delivery using nanofibers

The influence of different formulations and process parameters during the preparation of drug-loaded PLGA microspheres evaluated by multivariate data analysis

The main objective of this study was to evaluate the influence of the formulation and process parameters on PLGA microparticles containing a practically insoluble model drug (ibuprofen) prepared by the o/w solvent evaporation method. Multivariate data analysis was used. The effects of altered stirring speed of a mechanical stirrer (600, 1000 rpm), emulsifier concentrations (PVA concentration 0.1 %, 1 %) and solvent selection (dichlormethane, ethyl acetate) on microparticles characteristics (encapsulation efficiency, drug loading, burst effect) were observed. It was found that with increased stirring speed, the PVA concentration or the use of ethyl acetate had a significantly negative effect on encapsulation efficiency. In addition, ethyl acetate had an adverse effect on the burst effect, while the increased stirring speed had the opposite effect. Drug load was not affected by any individual variable, but rather by the interactions of evaluated variables

Czech republic and Brexit

Tématem diplomové práce je brexit a jeho dopady na Českou republiku. Velká Británie je pro Českou republiku významným obchodním i spojeneckým partnerem, což se může po brexitu výrazně změnit. Cílem práce je charakterizovat a analyzovat pravděpodobné dopady brexitu na Českou republiku ve vybraných oblastech, kterými jsou zahraniční obchod, víceletý finanční rámec, volný pohyb osob a nové rozložení pozic mezi jednotlivými členskými státy. Očekává se, že právě skrze tyto oblasti pocítí Česká republika dopady brexitu nejvíce.The topic of the thesis is brexit and its impacts on the Czech Republic. Great Britain is an important trading partner and ally for the Czech Republic which may change significantly after Brexit. The aim of the thesis is to characterize and analyze the probable impacts of Brexit on the Czech Republic in selected areas which are foreign trade, multiannual financial framework, free movement of people and new distribution of positions among individual member states. It is expected that it is through these areas that the Czech Republic will feel the effects of Brexit the most

Proposal to Improve the Marketing Strategy of the Company JUST CS, s.r.o.

The thesis focuses on the marketing strategy of the company JUST CS, s.r.o. Its aim is to analyze the current marketing strategy of the company JUST CS, s.r.o. focusing on the application of the marketing mix and SWOT analysis, and using my own field survey of customer satisfaction to provide suggestions and recommendations for improvement of the marketing strategy

Development of 3D Printed Multi-Layered Orodispersible Films with Porous Structure Applicable as a Substrate for Inkjet Printing

The direct tailoring of the size, composition, or number of layers belongs to the advantages of 3D printing employment in producing orodispersible films (ODFs) compared to the frequently utilized solvent casting method. This study aimed to produce porous ODFs as a substrate for medicated ink deposited by a 2D printer. The innovative semi-solid extrusion 3D printing method was employed to produce multilayered ODFs, where the bottom layer assures the mechanical properties. In contrast, the top layer provides a porous structure for ink entrapment. Hydroxypropyl methylcellulose and polyvinyl alcohol were utilized as film-forming polymers, glycerol as a plasticizer, and sodium starch glycolate as a disintegrant in the bottom matrix. Several porogen agents (Aeroperl® 300, Fujisil®, Syloid® 244 FP, Syloid® XDP 3050, Neusilin® S2, Neusilin® US2, and Neusilin® UFL2) acted as porosity enhancers in the two types of top layer. ODFs with satisfactory disintegration time were prepared. The correlation between the porogen content and the mechanical properties was proved. A porous ODF structure was detected in most samples and linked to the porogen content. SSE 3D printing represents a promising preparation method for the production of porous ODFs as substrates for subsequent drug deposition by 2D printing, avoiding the difficulties arising in casting or printing medicated ODFs directly

Influence of different formulations and process parameters during the preparation of drug-loaded PLGA microspheres evaluated by multivariate data analysis

The main objective of this study was to evaluate the influence of the formulation and process parameters on PLGA microparticles containing a practically insoluble model drug (ibuprofen) prepared by the o/w solvent evaporation method. Multivariate data analysis was used. The effects of altered stirring speed of a mechanical stirrer (600, 1000 rpm), emulsifier concentrations (PVA concentration 0.1 %, 1 %) and solvent selection (dichloromethane, ethyl acetate) on microparticle characteristics (encapsulation efficiency, drug loading, burst effect) were observed. It was found that with increased stirring speed, the PVA concentration or the use of ethyl acetate had a significantly negative effect on encapsulation efficiency. In addition, ethyl acetate had an adverse effect on the burst effect, while increased stirring speed had the opposite effect. Drug load was not affected by any particular variable, but rather by the interactions of evaluated variables

Targeting Human Thrombus by Liposomes Modified with Anti-Fibrin Protein Binders

Development of tools for direct thrombus imaging represents a key step for diagnosis and treatment of stroke. Nanoliposomal carriers of contrast agents and thrombolytics can be functionalized to target blood thrombi by small protein binders with selectivity for fibrin domains uniquely formed on insoluble fibrin. We employed a highly complex combinatorial library derived from scaffold of 46 amino acid albumin-binding domain (ABD) of streptococcal protein G, and ribosome display, to identify variants recognizing fibrin cloth in human thrombus. We constructed a recombinant target as a stretch of three identical fibrin fragments of 16 amino acid peptide of the Bβ chain fused to TolA protein. Ribosome display selection followed by large-scale Enzyme-Linked ImmunoSorbent Assay (ELISA) screening provided four protein variants preferentially binding to insoluble form of human fibrin. The most specific binder variant D7 was further modified by C-terminal FLAG/His-Tag or double His-tag for the attachment onto the surface of nanoliposomes via metallochelating bond. D7-His-nanoliposomes were tested using in vitro flow model of coronary artery and their binding to fibrin fibers was demonstrated by confocal and electron microscopy. Thus, we present here the concept of fibrin-targeted binders as a platform for functionalization of nanoliposomes in the development of advanced imaging tools and future theranostics