Enzymatic syntesis of flavonoid esters and controlled release from cosmetic formulation

• Main Author: Milivojević, Ana
• Other Authors: Bezbradica, Dejan, Pjanović, Rada, Knežević-Jugović, Zorica, Ćorović, Marija, Antov, Mirjana
• Format: Doctoral or Postdoctoral Thesis
• Language: unknown
• Published: Univerzitet u Beogradu, Tehnološko-metalurški fakultet 2019
• Subjects: flavonoids; lipase; esterification; immobilization; vagetable oils; diffusion; transdermal diffusion; cosmetic formulation; flavonoidi; lipaza; esterifikacija; imobilizacija; biljna ulja; transdermalna difuzija; kozmetiĉke formulacije; Antarc*; Antarctica
• Online Access: https://nardus.mpn.gov.rs/handle/123456789/17584; http://TechnoRep.tmf.bg.ac.rs/handle/123456789/4681; http://eteze.bg.ac.rs/application/showtheses?thesesId=7678; https://fedorabg.bg.ac.rs/fedora/get/o:22863/bdef:Content/download; http://vbs.rs/scripts/cobiss?command=DISPLAY&base=70036&RID=24141321; http://TechnoRep.tmf.bg.ac.rs/bitstream/id/2208/4678.pdf; https://hdl.handle.net/21.15107/rcub_nardus_17584

Within this doctoral dissertation, the possibility of efficient and economical enzymatic synthesis of esters of three flavonoids (floridzin, naringin and esculin) using different acyl donors and immobilized lipases B from C. antarctica as a biocatalyst was investigated. Additionally, transdermal diffusion characteristics of synthesized esters from various cosmetic formulations were determined. Synthesis of esters of the three aforementioned flavonoids using oleic acid as an acyl donor and Novozym® 435 as a biocatalyst was optimized and it was shown that the concentration of flavonoid and substrate molar ratio were two the most important factors influencing the synthesis process. The maximum conversion degree of all three flavonoids was achieved at a minimum initial flavonoid concentration, 10 mM. On the other hand, the optimum conditions for product yield as output depend on the acyl acceptor used, given that 30 mM and 70 mM were optimal concentrations of naringin and esculin for achieving the highest product yields. When it comes to the substrate molar ratio, it was shown that the large excess of oleic acid (1:18 for the conversion degree and 1:13 for the specific yield) was preferable for synthesis of floridzin-oleate, while for the esterification of other two flavonoids, five fold excess of oleic acid was optimal for high product yields. When it comes to the effect of fatty acids chain length (C2-C18) and unsaturation degree on floridzin-oleate synthesis, it was shown that high conversion degrees, over 70 % were obtained in reactions with all examined fatty acids. In order to develop the more economical process of flavonoid esterification, in the second phase od this thesis, alternative, cheaper acyl donors, such as triacetin and acetic anhydride for the synthesis of flavonoid acetate, and various vegetable oils (coconut, linseed and sunflower oil) for the synthesis of long chain fatty acid esters were examined. Triacetin proved to be the appropriate substrate for the synthesis of the acetyl derivative of ...