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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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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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Optimization of drug-loaded nanoparticles preparation
Kolářová, Adéla ; Holas, Ondřej (advisor) ; Paraskevopoulos, Georgios (referee)
Charles University Faculty of Pharmacy in Hradec Králové Department of Pharmaceutical Technology Consultant: PharmDr. Ondřej Holas, PhD. Student: Adéla Kolářová Title of Thesis: Optimization of drug-loaded nanoparticles preparation At the beginning of the work there are described various types of nanoparticles, the polymer particles are described in more detail, which is also dealt with in the experimental part. Furthermore, possible methods of preparation of polymer nanoparticles and their use in medicine are listed. Two methods of nanoparticles preparation from materials based on of poly (lactic-co-glycolic acid) were used. First method was emulsion-sonication, where the particles were formed using high frequency ultra-sound probe. The second method was spontaneous emulsification, where two solvents with different hydrophilicity were used. Different properties of resulting nanoparticles were assayed - size, polydisperzity, encapsulation efficacy, drug loading and recovery yield. Rhodamine B, a fluorescent dye, was used as a model substance for encapsulation experiments Nanoparticles were prepared from linear PLGA and PLGA branched by polyacrylic acid. Nanoparticles were stabilized by three different surfactants - poloxamer Pluronic® F127, polysorbate Tween® 20 and poly(vinyl)alcohol. Each...
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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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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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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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Pharmaceutical applications of polyesters as drug nanocarriers
Staňková, Petra ; Holas, Ondřej (advisor) ; Paraskevopoulos, Georgios (referee)
Charles University Faculty of Pharmacy in Hradci Králové Department of Pharmaceutical Technology Consultant: PharmDr. Ondřej Holas, PhD. Student: Petra Staňková Title of Thesis: Pharmaceutical applications of polyesters as drug nanocarriers Nanoparticles are nowadays intensively studied and perspective type of a drug carrier. Its potential is based on a possibility of targeted drug delivery and controlled drug release. The theoretical part is about nanoparticles types, polymers derived from α-hydroxyacids (PLA, PGA, PLGA). Focus is given on methods of nanoparticles preparation: dispersion of preformed polymers or the polymerization of monomers. The modification of particles surface and practical use of nanomedicine in healthcare are described in other chapters. The research in experimental part is focused on the influence of different types of PLGA and their weighing on the size, polydispersity, nanoparticles zeta potential and encapsulation efficiency of rhodamine B. Nanoparticles were prepared by nanoprecipitation method or by solvent evaporation method. The Zetasiser ZS 90 device was used to measure the size of the nanoparticles and to measure zeta potential. The result of the research shows the most suitable weighing for creation of nanoparticles is 25 mg. The samples of this weighing show a...
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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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Up-scaling and further development of matrix liposomes
Skalická, Veronika ; Paraskevopoulos, Georgios (advisor) ; Holas, Ondřej (referee)
Charles University, Faculty of Pharmacy in Hradec Králové Department of Pharmaceutical Technology Candidate: Veronika Skalická Supervisor: Dr. Georgios Paraskevopoulos, Ph.D.; Michael Binnefeld Title of Diploma thesis: Up-scaling and further development of matrix liposomes The thesis evaluates novel matrix liposomes formed by dual asymmetric centrifugation technology. Particles' parameters (size, size distribution and ζ-potential) were analyzed by dynamic light scattering method using ZetaSizer device. Encapsulation efficacy was determined by size exclusion chromatography using carboxyfluorescein as fluorescent encapsulation marker. The overall results support that the most beneficial formulation parameters are 15 min of speed mixing process with ceramic beads of diameter 1,0-1,2 mm. Up-scaling of the procedure didn't drastically affect liposomal parameters up to a lipid batch load of 700 mg. Furthermore, the usage of different types of gelatin or glycerinated gelatin didn't significantly influenced particles' characteristics. It is noteworthy that the matrix composed of 50% glycerinated gel sustained the ability to form liposomes by dispersion of vesicular phospholipid gels in phosphate buffer saline even after 31 days. Other matrices showed a damage of liposomes as confirmed by size and size...
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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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