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Transkarbam 12 and caffeine transdermal permeation from oleocreams. 1.
Štiková, Jana ; Berka, Pavel (advisor) ; Doležal, Pavel (referee)
The transdermal application of active substances and the related topic - skin barrier permeability were reviewed in theoretical part of this work. Present knowledge in transdermal permeation enhancers was then summarized shortly, with emphasis on Transkarbams and their development on the Faculty of Pharmacy of the Charles University. The results of the in vitro permeation experiments through full thickness pig ear skin are presented in the following experimental part. The acceleration effect of various concentrations of Transkarbam 12 (T12) on caffeine permeation from oleocreams containing 60% aqueous phase is evaluated. The following values of mean fluxes of caffeine Jr were found 7,88 ± 1,52 g.cm-2 .h-1 ; 9,34 ± 1,62 g.cm-2 .h-1 ; 10,89 ± 2,03 g.cm-2 .h-1 ; 11,29 ± 3,03 g.cm-2 .h-1 and 11,09 ± 2,21 g.cm-2 .h-1 for creams containing from creams containing 0%; 0,3%; 0,5%; 0,7% and 1% T12, respectively. Keywords: transdermal administration of active substances, skin barrier, transdermal permeation enhancers, Transkarbam 12.
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Ceramides and Dimethylamino Acid Derivatives as Skin Barrier Modulators
Novotný, Jakub ; Vávrová, Kateřina (advisor) ; Sedlák, Miloš (referee) ; Doležal, Pavel (referee)
The purpose of this work is to contribute to the understanding of the structure-activity relationships and behavior of the skin ceramides and transdermal penetration enhancers based on dimethylamino acid esters. First two chapters provide a theoretical background for understanding the main principles of transdermal drug delivery as well as composition and function of stratum corneum barrier. The experimental work is presented in the form of individual publications in chapters three to five. The first chapter describes transport routes through the human skin and gives an overview of enhancers of transdermal permeation with main accent on their chemical structure, mechanism of action, interaction with stratum corneum components and advantages and drawbacks of their use. The second chapter brings more detailed information on the specific content and composition of stratum corneum. The main attention is paid to the ceramides - a complex group of lipids that play a crucial role as cell signaling molecules and skin barrier constituents. In the skin, these sphingolipids form a major part of the stratum corneum intercellular lipid matrix, which is the barrier for penetration of most compounds. The development of such a protective layer was a critical step in the evolution of life on a dry land. Moreover,...
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Study of dispersity of nanoemulsive drug carriers
Hájková, Hana ; Doležal, Pavel (advisor) ; Vachek, Josef (referee)
SUMMERY Theoretical part of this work is focused on explanation of such terms like nanoparticules and nanoemulsions and their usage within peroral and topical administration. Next part explains the merit of zeta potential and DLVO theory, which influence the stability of the elements. Off course, also the principle of the measuring of viscosity is mentioned, because viscosity is taken into consideration in case of measuring of the element dispersion. The experimental part is focused on determination of the partije size by photon correlation spectroscopy by temperature of 25řC and 37řC. The measurement was taken in chronological succession to estimate the stability of dispersion system. It was also measured electrokinetic parameter - zeta potential, which plays a fundamental role by keeping the stability of nanoemulsions. It was proved, that the size of the elements gets settled after approx. 1 week, further changes are not so striking anymore, not even by the increase of temperature to 37řC. Since creating the emulsion (approx. 1 week), the major share of the size of particles (about 60-95%) was ranging between 120-175 nm. As well zeta potencial remains in stable range (+2 mV - -0,6 mV) by the increase of temperature to 37řC and adding of three pH highs of buffers. From the gained results we can draw...
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Methodical study of surface tension of epidermal lipids
Lasák, Roman ; Doležal, Pavel (advisor) ; Musilová, Marie (referee)
The theoretical part brings a brief overview of selected relevant papers dealing with measurements of advancing and receding contact angles. These studies deal with the methods of determination of free surface energy, determination of contact angles, estimation of free equilibrium surface energy components, changes in the level of components of free surface skin energy following washing, Marangoni effect in water, advancing, receding and equilibrium contact angles, measurement of dynamic adhesive tension and dynamic contact angles. In the experimental part, the Krüss K100 tensiometer equiped with the plate method was used to measure the surface tension and contact angles of distilled water at 37řC on the surfaces impregnated with examined substances in selected proportions and dissolved in volatile solvent. The measuring plate surface was impregnated with prepared samples in advance; the first samples: palmitic acid and oleic acid with cholesterol; the second samples: cholesterol sodium sulphate in mixtures with cholesterol and selected fatty acid, as well as in combination with cholesterol, 14S24 and oleic acid; the third samples: N-acetyl-D-sphingosin, N-hexanoyl-D- sphingosin, 12SG12, 12GV12 in the solution alone, as well as in combinations with cholesterol and in combination with cholesterol...
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The phase behaviour of lipidic models of stratum corneum
Kafková, Veronika ; Musilová, Marie (advisor) ; Doležal, Pavel (referee)
From the 50s to the 70s it has been shown that the human skin barrier primarily is located at the extracellular lipid matrix of stratum corneum. The barrier capacity is a function of the physical state and structural organization of extracellular lipid matrix. The lipid matrix is essentially composed of very long chain saturated ceramides, cholesterol and free fatty acids. Since then several models for the structure and function of the mammalien skin barrier have been proposed, but some main unsolved problems with respect to lipid organization still exit. Whether the extracellular lipid matrix is constituted by single gel-phase or if there is a coexistence of several crystalline (solid) and gel-phases, whether a separate fluid phase is present? Such a theoretical model may provide for a rational design of experimental studies on skin diseases, skin permeability, topical drug administration, skin protection, etc. In this work we are using differential scanning calorimetry (DSC) to analyse the thermotropic phase behavior of cholesterol, synthetic ceramid and in vitro prepared mixtures composed of cholesterol, synthetic ceramid and oleic acid. We are using simplified models and we focus on the sample preparation method and on the effects of substances on the phase behaviour of the model. The aim of...
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Characterisation of Rat Alveolar Cell Line R3/1
Horálková, Lenka ; Doležal, Pavel (advisor) ; Fendrich, Zdeněk (referee) ; Forbes, Ben (referee)
The rat cell line R3/1 displays several phenotypical features of alveolar epithelial type I cells. In order to characterise the cell line as an in vitro model for drug disposition studies, R3/1 cells were cultured on Transwell filters and the transepithelial electrical resistance (TEER) was measured as a parameter for the integrity of cell layers. Presence of cell junctional proteins (i.e., E-cadherin, occludin, ZO-1 and ZO-2) was studied on mRNA (by reverse transcriptase-polymerase chain reaction, RT-PCR) and antigen level (by immunofluorescence microscopy, IFM). Moreover, the expression pattern of catabolic peptidases (carboxypeptidase M, aminopeptidases A, B, N and P, γ-glutamyltransferase, dipeptidylpeptidase IV, angiotensin-converting enzyme, and endopeptidases 24.11 and 24.15) was analysed in R3/1 cells and compared to rat alveolar epithelial I-like cells in primary culture. TEER values were peaking at ~99±17 Ω cm2 after 5 days in culture. Addition of 0.1 µM dexamethasone together with foetal bovine serum at 20% increased TEER by 65%. However, none of culture conditions used in our study yielded monolayers with TEER values comparable to those of primary cultures of rat pneumocytes. RT-PCR revealed the absence of transcripts encoding for E- cadherin and occludin. However, ZO-1 and -2 mRNA transcripts...
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Transdermal in vitro permeation of cyclosporine. III.
Krejčová, Hana ; Doležal, Pavel (advisor) ; Zbytovská, Jarmila (referee)
Diploma Thesis, Hana Krejčová 2006 Abstract The theoretical part of thesis provides a brief overview of the transdermal administration of drugs, including the use of transdermal enhancer. Part concerning the CyA includes information about its structure, pharmacological effects, including adverse effects, its use in therapy and application possibilities. Experimental section presents the results of in vitro permeation experiments on pig skin. Acceptor phase consisted of propylene glycol and Tris-buffer pH 7.1 at a 1:1 ratio. The permeant determination was performed by HPLC with UV detection at 220 nm. It was confirmed that the choice of the acceptor and the mobile phase was appropriate. As a donor samples were used supersaturated CyA systems without enhancer, and also with the addition of 5% or Azone, methyl pyrrolidone or dodecyl pyrrolidone, or 1% of transkarbam 12. All the enhancers in the concentrations increase depot formation in skin, transkarbam 12 although used in the lowest concentration did it most.
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Mechanismy průniku sylicylátů monovrstvami buněk Caco-2: zapojení transportních proteinů.
Čierný, Jakub ; Doležal, Pavel (advisor) ; Šnejdrová, Eva (referee)
The aim of this work is to study properties of the transport of salicylic acid and its derivates across Caco-2 cell monolayers, an influence of possible inhibitors of cell transportation and a brief review of related issues. The influence of substance, which opens tight junctions between Caco-2 cells, so called absorption enhancers, is also examined. The main goal is to find out, what kind of transport takes the main part in salicylic acid transport and to compare the results to the data obtained using gentisic and 5-hydroxyisophthalic acid, and, at the same time, to study the influence of ethylenediaminetetraacetic acid as an absorption enhancer and to compare possible inhibitive effect of several compounds. It was assumed that both passive and active transport take part in the transport of salicylic acid. The theoretical part of the thesis briefly summarizes chemical substances properties, which have an influence on their transport across cell membranes, introduces Caco-2 cells as an important instrument of drug absorption and distribution research, defines the individual types of cell transports and describes the types of transporter proteins which can be localized on the Caco-2 cell membrane. The experimental part of the work describes the technique of Caco-2 cells cultivation and the process of...
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Transdermal in vitro permeation of methoxytacrine. III.
Režňáková, Eva ; Doležal, Pavel (advisor) ; Bajgar, Jiří (referee)
Diploma Thesis 2006, Eva Režňáková Abstract The theoretical part gives a list of selected issues on transdermal drug delivery and summarizes information on Azone, including new technical information published in 2005. In vitro permeation experiments using the excised pig skin confirm the considerable potential for transdermal administration of 7-methoxytacrine. Using the isopropyl myristate as a vehicle the therapeutically valuable fluxes at about 15 [μg/cm2.h-1] were obtained. Transdermal acceleration and impact of 5% added amounts of methyl pyrrolidone and dodecyl pyrrolidone were not established. As a promising in this respect appears to use Azone and transkarbam 12.
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