Studium konjugátů sfingolipidů s kyselinou hyaluronovou a jejich aplikace na kůži

Juhaščik, Martin

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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