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Synthesis of ceramide analogs with various sphingosine length and evaluation of their effects on the skin barrier
Školová, Barbora ; Vávrová, Kateřina (advisor) ; Hrabálek, Alexandr (referee)
Ceramides are a complex group of lipids, naturally occurring in the uppermost layer of the epidermis, in the stratum corneum (SC). They constitute a major component of extracellular matrix and they are responsible for the skin barrier properties. Diseases such as atopic dermatitis or psoriasis are associated with the decline in content and changes in the composition of ceramides, which lead to the reduction in the protective functions of the skin. Although the importance of ceramides is known, the relationship between their structure and effect on the barrier function is not yet fully elucidated. Earlier studies indicate that the length of ceramide acyl chain affects the skin permeability. It appears that ceramides with short acyl lose the protective properties. First, I have prepared a series of analogues of ceramides with fifteen carbon atoms chain in the sphingosine part and the acyl part of a length of 2, 4 and 6 carbons. Starting substance of the synthesis was N-protected L-serine methyl ester, which was further protected by the formation of a cyclic acetal and subjected to the reduction of the ester to aldehyde. The resulting aldehyde reacted with 1-alcynide in the presence of HMPA. The triple bond was subsequently reduced to a trans-double bond by lithium in ethylamine. After deprotection of...
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Study of skin barrier defects by lipid monolayers
Nováčková, Anna ; Školová, Barbora (advisor) ; Vraníková, Barbora (referee)
Charles University in Prague, Faculty of Pharmacy in Hradec Králové Department of Pharmaceutical Technology Author: Anna Nováčková Supervisor: Mgr. Barbora Školová, Ph.D. Title of thesis: Study of skin barrier defects by lipid monolayers Ceramides (Cer) together with free fatty acids and cholesterol form the intercellular space of the uppermost skin layer, the stratum corneum (SC). This lipid matrix presents the skin barrier, which protects human organism from environmental factors (endogenous substances, physical radiation) as well as prevents the body from water loss. Cer are synthetized from polar precursors: glucosylated Cer (GCer) and sphingomyelins by splitting the polar part by the hydrolytic enzymes β-glucocerebrosidase (β-GCer-ase) and sphingomyelinase. A lack of these enzymes leads to accumulation of precursors and a non-functional skin barrier is formed. The goal of this work was to study the β-GCer-ase defects by monolayer lipid models of the SC. The impact of GCer quantity on lipids organisation was evaluated by several techniques (Langmuir monolayers at the gas-liquid interface, Brewster angle microscopy and atomic force microscopy). At the gas - liquid interface mixtures with precursor do not organise spontaneously at lower surface pressures (1.5 mN/m). However, with increasing...
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Study of skin diseases using monolayer lipid models
Mihalová, Veronika ; Školová, Barbora (advisor) ; Holas, Ondřej (referee)
Charles University, Faculty of Pharmacy in Hradec Králové Department of Pharmaceutical Technology Consultant: PharmDr. Barbora Školová, Ph.D. Student: Veronika Mihalová Title of Thesis: Study of skin diseases using monolayer lipid models Skin is an organ that protects the body against external influences and excessive water loss. The proper skin barrier is localized in the outermost layer of the epidermis, the stratum corneum (SC). The function of this barrier depends on the composition and organization of the extracellular space of SC. It consists mainly of ceramides (CER), free fatty acids and cholesterol in approximately equimolar ratio. Imbalances in the lipid composition are associated with skin diseases such as atopic dermatitis. Ceramidase is an enzyme which cleaves CER or glucosylated ceramides (precursor of CER) to lysosphingolipid (LysoSph) and fatty acid. Abundance or deficit of this enzyme causes dysfunction of skin barrier and the manifestation of skin diseases, e.g. Farber's disease. The aim of this work was to study the monolayer lipid models whose compositions reflect the abundance of ceramidase in the skin. Lipid models were studied by Langmuir monolayers at the air-liquid interface and at the solid surface, including Brewster angle microscopy and atomic force microscopy. With...
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Determination of flowable liquid retention potential of Aeroperl® for three hydrophilic solvents
Macharová, Květa ; Vraníková, Barbora (advisor) ; Školová, Barbora (referee)
Charles University in Prague, Faculty of Pharmacy in Hradec Králové Department of: Pharmaceutical Technology Candidate: Květa Macharová Supervisor: PharmDr. Barbora Vraníková, Ph.D. Title of Diploma Thesis: Determination of flowable liquid retention potential of Aeroperl ® for three hydrophilic solvents Preparation of modern dosage form called liquisolid systems may lead to the increased bioavailability of poorly water-soluble drugs. The main principle of their preparation is conversion of the drug in the liquid form to a dry non-adhesive powder with properties suitable for further processing. However, each powder is able to retain only a certain amount of liquid while maintaining appropriate flow properties and compressibility. The objective of this diploma thesis was to determine the flowable liquid retention potential of Aeroperl® 300 for three non-volatile solvents (polyethylene glycol 200 and 400 and propylene glycol). The value of flowable retention potential of Aeroperl® 300 was established to 0.5, 0.44 and 0.36 for propylene glycol, polyethylene glycol 400 and polyethylene glycol 200, respectively.
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Study of monolayer lipid models of skin barrier diseases
Doláková, Andrea ; Školová, Barbora (advisor) ; Svačinová, Petra (referee)
Charles University, Faculty of Pharmacy in Hradec Králové Department of Pharmaceutical Technology Author: Andrea Doláková Supervisor: PharmDr. Barbora Školová, Ph.D. Title of thesis: Study of lipid monolayer models of skin barrier diseases Skin protects human body from external factors and maintain internal integrity of organism. Skin barrier is formed by corneocytes and lipid matrix in intercellular space of stratum corneum, the uppermost layer of epidermis. Lipid matrix consists of ceramides, free fatty acids and cholesterol. The composition and organisation of lipid matrix are essential for the skin barrier properties. Ceramides are synthetized from glucosylated ceramide and sphingomyelin by hydrolitic enzymes β-glucocerebrosidase and sphingomyelinase. Insufficiency or malfunction of these enzymes lead to functionless skin barrier. The aim of this work was to prepare and study monolayer lipid models, which simulated the malfunction of sphingomyelinase in skin diseases. For valuation we used several techniques such as Langmuir monolayers, Brewster angle microscopy (at the air-liquid interface), Langmuir-Blodgett technique and atomic force microscopy. Monolayers with 100% substitution of sphingomyelin layout the most readily with rising surface pressure and the course of their isotherm is very...
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Synthesis and study of ceramide analogues
Školová, Barbora ; Vávrová, Kateřina (advisor) ; Matějka, Pavel (referee) ; Šklubalová, Zdeňka (referee)
Charles University in Prague, Faculty of Pharmacy in Hradec Králové Department of inorganic and organic chemistry Candidate: Mgr. Barbora Školová Supervisor: doc. PharmDr. Kateřina Vávrová, Ph.D. Title of doctoral thesis: Synthesis and study of ceramide analogues Ceramides (Cer) together with free fatty acids and cholesterol form intercellular lamellar space of the uppermost skin layer (stratum corneum, SC). This lipid matrix presents the proper skin barrier - it protects organism against outer environment and keeps its homeostasis as well. The composition and arrangement of the intercellular lipid matrix is essential for the skin barrier properties. In spite of this fact, the organization of SC lipids at the molecular level is not fully elucidated. The aim of this work is to contribute to more detailed insight into organization of skin barrier using SC lipid model membranes, in particular to find the structural parameters in ceramide molecules, which play a role in the maintenance of the skin barrier. The SC model membranes present a useful tool to study SC lipids, they mimic physiological or pathological conditions in the skin. The obtained results should be used in diagnosing or therapy of skin diseases characteristic with impaired barrier function, such as atopic dermatitis or psoriasis....
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Study of skin barrier defects by lipid monolayers
Nováčková, Anna ; Školová, Barbora (advisor) ; Vraníková, Barbora (referee)
Charles University in Prague, Faculty of Pharmacy in Hradec Králové Department of Pharmaceutical Technology Author: Anna Nováčková Supervisor: Mgr. Barbora Školová, Ph.D. Title of thesis: Study of skin barrier defects by lipid monolayers Ceramides (Cer) together with free fatty acids and cholesterol form the intercellular space of the uppermost skin layer, the stratum corneum (SC). This lipid matrix presents the skin barrier, which protects human organism from environmental factors (endogenous substances, physical radiation) as well as prevents the body from water loss. Cer are synthetized from polar precursors: glucosylated Cer (GCer) and sphingomyelins by splitting the polar part by the hydrolytic enzymes β-glucocerebrosidase (β-GCer-ase) and sphingomyelinase. A lack of these enzymes leads to accumulation of precursors and a non-functional skin barrier is formed. The goal of this work was to study the β-GCer-ase defects by monolayer lipid models of the SC. The impact of GCer quantity on lipids organisation was evaluated by several techniques (Langmuir monolayers at the gas-liquid interface, Brewster angle microscopy and atomic force microscopy). At the gas - liquid interface mixtures with precursor do not organise spontaneously at lower surface pressures (1.5 mN/m). However, with increasing...
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The antiinflammatory effects of creams based on a pomegranate extract and their penetration to the skin
Rudecká, Kateřina ; Vávrová, Kateřina (advisor) ; Školová, Barbora (referee)
Charles University in Prague Faculty of Pharmacy in Hradec Králové Department of Inorganic and Organic Chemistry Cardiff University, Cardiff School of Pharmacy and Pharmaceutical Sciences, Drug Delivery Department, Wales, United Kingdom Candidate: Kateřina Rudecká Supervisor: Doc. PharmDr. Kateřina Vávrová, Ph.D Dr. Charles M. Heard, Ph.D. Title of diploma thesis: The anti-inflammatory effects of creams based on a pomegranate extract and their penetration to the skin. To affected people, inflammatory skin diseases mean an unpleasant life experience. Unfortunately, side effects of currently the most widely used drugs for skin diseases - topically applied corticosteroids, are also often involved. That is probably why we can see a growth in the popularity of natural products in recent years. Among these hidden and newfound treasures undoubtedly belongs pomegranate, a fruit used for thousands of years and now again popularized for its antioxidant, anti-inflammatory and anticancer properties. In this study, we formulated creams consisting of Emulsifying ointment BP 15% w/w as an excipient in combination with various oils, with a focus on pomegranate seed oils (PSO, manufactured one and bought one), constituting 15% w/w. The aqueous phase containing pomegranate rind extract (PRE) made 70% w/w. These...
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Synthesis of ceramide analogs with various sphingosine length and evaluation of their effects on the skin barrier
Školová, Barbora ; Vávrová, Kateřina (advisor) ; Hrabálek, Alexandr (referee)
Ceramides are a complex group of lipids, naturally occurring in the uppermost layer of the epidermis, in the stratum corneum (SC). They constitute a major component of extracellular matrix and they are responsible for the skin barrier properties. Diseases such as atopic dermatitis or psoriasis are associated with the decline in content and changes in the composition of ceramides, which lead to the reduction in the protective functions of the skin. Although the importance of ceramides is known, the relationship between their structure and effect on the barrier function is not yet fully elucidated. Earlier studies indicate that the length of ceramide acyl chain affects the skin permeability. It appears that ceramides with short acyl lose the protective properties. First, I have prepared a series of analogues of ceramides with fifteen carbon atoms chain in the sphingosine part and the acyl part of a length of 2, 4 and 6 carbons. Starting substance of the synthesis was N-protected L-serine methyl ester, which was further protected by the formation of a cyclic acetal and subjected to the reduction of the ester to aldehyde. The resulting aldehyde reacted with 1-alcynide in the presence of HMPA. The triple bond was subsequently reduced to a trans-double bond by lithium in ethylamine. After deprotection of...
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Synthesis and study of ceramide analogues
Školová, Barbora ; Vávrová, Kateřina (advisor) ; Matějka, Pavel (referee) ; Šklubalová, Zdeňka (referee)
Charles University in Prague, Faculty of Pharmacy in Hradec Králové Department of inorganic and organic chemistry Candidate: Mgr. Barbora Školová Supervisor: doc. PharmDr. Kateřina Vávrová, Ph.D. Title of doctoral thesis: Synthesis and study of ceramide analogues Ceramides (Cer) together with free fatty acids and cholesterol form intercellular lamellar space of the uppermost skin layer (stratum corneum, SC). This lipid matrix presents the proper skin barrier - it protects organism against outer environment and keeps its homeostasis as well. The composition and arrangement of the intercellular lipid matrix is essential for the skin barrier properties. In spite of this fact, the organization of SC lipids at the molecular level is not fully elucidated. The aim of this work is to contribute to more detailed insight into organization of skin barrier using SC lipid model membranes, in particular to find the structural parameters in ceramide molecules, which play a role in the maintenance of the skin barrier. The SC model membranes present a useful tool to study SC lipids, they mimic physiological or pathological conditions in the skin. The obtained results should be used in diagnosing or therapy of skin diseases characteristic with impaired barrier function, such as atopic dermatitis or psoriasis....
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