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Study of conjugates of sphingolipids with hyaluronic acid and their application on the skin
Juhaščik, Martin ; Kováčik, Andrej (advisor) ; Gajdziok, Jan (referee) ; Miletín, Miroslav (referee)
1 ABSTRACT Charles University, Faculty of Pharmacy in Hradec Králové Training Workplace Department of Pharmaceutical Technology Doctoral Degree Program Pharmaceutical Technology Candidate Mgr. Martin Juhaščik Supervisor doc. PharmDr. Andrej Kováčik, Ph.D. Advisor Gloria Huerta-Ángeles, Ph.D. Title of Doctoral Thesis Study of conjugates of sphingolipids with hyaluronic acid and their application on the skin The main goal of this study was to systematically design and subsequently prepare conjugates of hyaluronic acid (HA) with selected sphingolipids, which could find application in their topical administration during physiological decline of skin functions. In this study, phytosphingosine and ceramide were chemically linked to HA via biocompatible linkers, enabling successful modification of HA into a hydrophobized conjugate of sphingolipid-linker-hyaluronate. The preparation of succinylceramide-hyaluronate conjugate was found to be the most effective. The developed method of preparing the conjugate using mixed anhydrides brings several advantages, including the possibility of scaling up the preparation and conducting reactions in an aqueous environment. The method was effective over a wide range of molecular weights, from 6 to 442 kgmol-1, achieving a degree of substitution of up to 14.2 %, surpassing 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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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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