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Study of the effect of cholesterol concentration on monolayer models
Šrámová, Eliška ; Paraskevopoulos, Georgios (advisor) ; Svačinová, Petra (referee)
Charles University, Faculty of Pharmacy in Hradec Králové Department of Pharmaceutical Technology Author: Eliška Šrámová Supervisor: Dr. Georgios Paraskevopoulos, Ph. D Consultant: Mgr. Anna Nováčková Title of Thesis: Study of the effect of cholesterol concentration on monolayer models Skin is composed of 3 major layers: hypodermis, dermis, and epidermis. The uppermost layer, which is called stratum corneum (SC), has a unique structure resembling a well-built wall. Corneocytes represent bricks and the lipid matrix works like a mortar. Ceramides, free fatty acids, and cholesterol (Chol) are the main lipids creating the human SC matrix. In a healthy SC, the ratio of these lipids is equimolar. This ratio is crucial, not only to maintain the barrier function of the skin, but also for the organization of lipids in SC. Chol appears to be required for the correct lamellar organization, and the ordering of lipids inside of the lamellar formation (lateral organization) in SC. Abnormalities in the ratio of the lipids and depleted amount of Chol can lead to a disruption of the skin barrier function resulting in skin disease or multisystemic diseases (e.g. X-linked ichthyosis, Conradi-Hünermann-Happle syndrome, and CHILD syndrome.) The present work deals with a Chol deficiency study on lipid organization on...
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Novel amino-decorated polyamidoamine dendrimers with ethylenediamine core: Synthesis and potential application in (trans)dermal drug delivery
Langerová, Martina ; Paraskevopoulos, Georgios (advisor) ; Kováčik, Andrej (referee)
Dendrimers are characterized as synthetic, spherical macromolecules with tree- like branched structures. Their well-controlled sizes (3 - 10 nm), ease of functionalization, high water solubility, well-defined chemical structure, and biocompatibility make these nanomaterials attractive for a wide spectrum of promising biomedical applications. Peptide dendrimers and polyamidoamine (PAMAM) dendrimers have been used to date as effective transdermal or topical drug delivery systems, with the latest in a much greater extent. The structural characteristics of the aforementioned molecules guided us to design a novel repeating unit for dendrimers (monomer) possessing amino branching point and able to afford generation expanding through repeating amide bonds. The novel monomer, after appropriate modifications, was used to develop lower generations of polyamidoamino dendritic structures having amide groups and amino-branching points in their interior. The new dendrimers were isolated and fully characterized by typical spectroscopic technics. The final molecules will be used in human skin permeation experiments and will be evaluated for their effect on skin permeability.
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Polymeric stabilizers maintaining the supersaturation solubility of itraconazole nanocrystals after dissolution process
Kubačková, Jana ; Holas, Ondřej (advisor) ; Paraskevopoulos, Georgios (referee)
Title of thesis: Polymeric stabilizers maintaining the saturation solubility of itraconazole nanocrystals after dissolution process Author: Jana Kubačková Department: Pharmaceutical Technology Supervisor: PharmDr. Ondřej Holas, Ph.D. Specialized supervisor: Assoc. Prof. Leena Peltonen, Ph.D. The increase of bioavailability of poorly water soluble drugs is still an issue. One of the techniques improving aqueous drug substance solubility, and consequently enhancing bioavailability, is formation of nanoparticles. However, the bioavailability is determined by the concentration of the dissolved drug achieved at the time of absorption. This fact emphasizes the importance of the maintenance of the high solubility until the absorption area is reached. Sufficiently stabilised nanocrystalline drugs offer a solution to this problem. In this thesis, the solid nanoparticle formations of an antifungal agent itraconazole (ITZ) are presented. Wet milling was employed to create the nanosuspension stabilised by binary mixture of stabilisers or by a single stabiliser. An aggregation inhibitor Poloxamer 407 (F127) in the combination with a polymeric precipitation inhibitor hydroxypropyl methylcellulose (HPMC) or polyvinyl pyrrolidone (PVP) at different ratios, or a single precipitation inhibitor, were utilised. The...
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Study of microstructure of skin barrier model using deuterated ceramides
Juhaščik, Martin ; Kováčik, Andrej (advisor) ; Paraskevopoulos, Georgios (referee)
Charles University, Faculty of Pharmacy in Hradec Králové Department of Pharmaceutical Technology Author: Martin Juhaščik Supervisor: PharmDr. Andrej Kováčik, Ph.D. Title of diploma thesis: Study of microstructure of skin barrier model using deuterated ceramides Ceramides (Cer) are sphingolipids, which participate in eucaryotic cells in various biological processes (cell signalling, proliferation, differentiation and cell apoptosis). In mammalian skin, Cer are localized in the uppermost layer of epidermis, stratum corneum (SC). In this layer, Cer along with cholesterol (Chol) and free fatty acids form multilayer lamellae of intercellular lipid matrix. The skin lipid arrangement in SC is still unclear. To evaluate the skin lipid arrangement, skin membrane models with labelled (deuterated) lipids have been used. Therefore, the aim of this work was to synthesize sphingosine with deuterated chain and Cer based on deuterated sphingosine, i.e., N-lignoceroyl sphingosine-d28 (with lignoceric acid acyl (C24); d-CerNS) and N-lignoceroyl-d47 sphingosine-d28 (dd-CerNS) and to study their phase behaviour and arrangement in model membranes by using biophysical studies. Synthesis of deuterated Cer started from elimination of 1-pentadecanol-d31 to obtain a deuterated terminal alkene. Next, a vinylation of...
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Formulation and trans(dermal) delivery of liposomes containing imiquimod
Tirala, Petr ; Švecová, Barbora (advisor) ; Paraskevopoulos, Georgios (referee)
Charles University, Faculty of Pharmacy in Hradec Králové Department of Pharmaceutical Technology Author: Petr Tirala Supervisor: PharmDr. Barbora Švecová, Ph.D. Title of thesis: Formulation and (trans)dermal application of liposomes containing imiquimod Imiquimod (IMQ), a substance belonging to the class of heterocyclic imidazoquinolines, shows significant immunomodulatory effects after topical administration, which is used to treat a variety of viral and malignant diseases of the skin. IMQ is currently used in clinical practice in the form of cream Aldara® containing 5% of active substance, which is unstable and irritating and after removal from the skin IMQ poses an ecological load for the environment. The aim of this thesis was preparation of liposomes for topical administrativ containing lower - 1% amount of IMQ and evaluation of penetration of IMQ into human skin in vitro. To improve the properties of liposomes and promote patency of the active ingredient through the skin barrier to the deeper skin layers various additives were used. Permeation experiments were carried out in Franz diffusion cells on the human skin in order to create the conditions that are as physiological as possible. Amount of IMQ was determined in the uppermost layer of the skin, epidermis, dermis, acceptor phase...
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Formulation of Imiquimod loaded liposomes in the presence of dendrimers
Štěpničková, Tereza ; Paraskevopoulos, Georgios (advisor) ; Paraskevopoulou, Anna (referee)
Charles University, Faculty of Pharmacy in Hradec Králové Department of Pharmaceutical Technology Supervisor: Dr. Georgios Paraskevopoulos, Ph.D. Consultant: Eleni Panoutsopoulou Author: Tereza Štěpničková Title of the thesis: Formulation of Imiquimod loaded liposomes in the presence of dendrimers Dendritic molecules, as highly branched polymers, are very attractive nanosystems for broad biomedical applications. Their specific properties include the ability to increase transdermal permeation of active ingredients as well as the ability to increase the water solubility of poorly soluble drugs. The main purpose of this thesis was the utilization of dendrimers to raise the concentration of the chemoterapeutic drug imiquimod inside liposomal formulations. Solutions of dendritic molecules zero, first, second and third generation were prepared, each at concentrations of 5 mg/ml and 10 mg/ml. These were subsequently used for the hydration of thin film lipid during the preparation of liposomes with the encapsulated drug. Two methods of the incorporation of imiquimod to liposomes were used. The first method represented insertion of the drug to lipids, the second was dissolution of the drug in the dendrimer solution. The concentration of encapsulated imiquimod, including the encapsulation efficacy, was...
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Formulation of Imiquimod loaded liposomes in the presence of dendrimers
Štěpničková, Tereza ; Paraskevopoulos, Georgios (advisor) ; Nováčková, Anna (referee)
Charles University, Faculty of Pharmacy in Hradec Králové Department of Pharmaceutical Technology Supervisor: Dr. Georgios Paraskevopoulos, Ph.D. Consultant: Eleni Panoutsopoulou Author: Tereza Štěpničková Title of the thesis: Formulation of Imiquimod loaded liposomes in the presence of dendrimers Dendritic molecules, as highly branched polymers, are very attractive nanosystems for broad biomedical applications. Their specific properties include the ability to increase transdermal permeation of active ingredients as well as the ability to increase the water solubility of poorly soluble drugs. The main purpose of this thesis was the utilization of dendrimers to raise the concentration of the chemoterapeutic drug imiquimod inside liposomal formulations. Solutions of dendritic molecules zero, first, second and third generation were prepared, each at concentrations of 5 mg/ml and 10 mg/ml. These were subsequently used for the hydration of thin film lipid during the preparation of liposomes with the encapsulated drug. Two methods of the incorporation of imiquimod to liposomes were used. The first method represented insertion of the drug to lipids, the second was dissolution of the drug in the dendrimer solution. The concentration of encapsulated imiquimod, including the encapsulation efficacy, was...
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Formulation and characterization of oxims loaded PLGA nanoparticles
Hafezi, Ramin ; Šnejdrová, Eva (advisor) ; Paraskevopoulos, Georgios (referee)
Thesis title: Formulation and characterization of oxime loaded PLGA nanoparticles Author: Ramin Hafezi Supervisor: PharmDr. Eva Šnejdrová, Ph.D. Advisor: PharmDr. Juraj Martiška, Ph.D. Department: Department of Pharmaceutical Technology The diploma thesis was focused on PLGA nanoparticles (NPs) which could be loaded with oximes, prepared by a double emulsion technique, and characterised by size, polydispersity and zeta potential. The theoretical part deals with the most common methods of the NPs preparation, the polymers and stabilizers employed, and drug delivery to brain. In the experimental part the effect of various formulation factors on NP characteristics were studied: linear or branched PLGA derivative, the concentrations of polymer, the volumes of primary emulsion. Dichloromethane (DCM) or Dimethyl sulfoxide (DMSO) as solvent for polymers were used and Poloxamer 407 or Didodecyldimethylammonium bromide (DDAB) as an outer phase stabilizer were employed. By comparison among the collected results, it seemed 1% A2 in DMSO and stabilization with poloxamer 407 could be best candidate for the oxime loaded drug delivery systems as it was possible to produce nanoparticles with size from 152 to 168 nm with PDI of below 0.15. Electrostatic stability in case of using DDAB was resulted excellent and...
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Characterization of PLGA-based film forming systems
Věříš, Andrea ; Šnejdrová, Eva (advisor) ; Paraskevopoulos, Georgios (referee)
Title of thesis: Characterization of PLGA-based film forming systems Author: Mgr. Andrea Věříš Department: Department of Pharmaceutical Technology Supervisor: PharmDr. Eva Šnejdrová, Ph.D. The aim of this thesis is to review available sources on film forming systems (FFSs), to test characteristics of poly(lactic-co-glycolic acid) of low molar mass linear or branched configuration in combination with multifunctional plasticizers and to formulate salicylate loaded film forming system. The theoretical section is focused on general characteristics and excipients used for FFs formulation and testing methods. Besides that, mathematical models commonly used for evaluation of flow behaviour are included. In the experimental section, effects of plasticizers ethyl pyruvate, methyl salicylate and triacetin on the rheological and adhesive properties of the polyesters were tested to select the optimal combination. All tested plasticizers decrease the viscosity of the polymers with ethyl pyruvate being the most effective. The flow curves of plasticized PLGA were analysed to Power law and Newton models revealing the Newton character of the systems. The evaluation of viscoelastic behavior showed liquid-like characteristic of these systems. The adhesive properties were determined by the pull away test providing the...
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Effect of the concentration of amino-decorated polyamidoamine dendrimers with ethylenediamine core at the (trans)dermal delivery of 5-fluorouracil
Chladová, Pavlína ; Paraskevopoulos, Georgios (advisor) ; Holas, Ondřej (referee)
Effect of the concentration of amino-decorated polyamidoamine dendrimers with ethylenediamine core at the (trans)dermal delivery of 5-Fluorouracil Pavlína Chladová Dendrimers are synthetic, symmetrically tree-like branched molecules. They are composed of repeating units (monomers). They have high density of surface functional groups and spherical shape in solution. Since their molecular weight is highly controllable, they are characterized by monodispersity and this is their main difference from classical polymers. Dendrimers have a wide spectrum of applications in biomedicine. Due to the empty space between the branches of the molecule, they can encapsulate drugs, and by conjugation and complexation to the surface groups, they are able to carry even larger drug molecules. Thus, dendrimers can be used as drug delivery systems. In addition, they have been used for skin application of several active molecules, either as topical or transdermal delivery. Suitable properties for (trans)dermal application have been demonstrated for dendrimers which consist of monomers with amine groups and are connected with amide bonds. The goal of this thesis was the preparation of dendrimers with these characteristics and the evaluation of their concentration influence to the permeability of 5-Fluorouracil (5-FU) to human...
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