Monika Kopečná1, Miloslav Macháček2, Eva Prchalová3, Petr Štěpánek4, Pavel Drašar4, Martin Kotora3,5, Kateřina Vávrová6. 1. Skin Barrier Research Group,, Charles University, Faculty of Pharmacy in Hradec Králové,, Akademika Heyrovského 1203,, 50005, Hradec Králové, Czech Republic. 2. Department of Biochemical Sciences,, Charles University Faculty of Pharmacy in Hradec Králové,, Akademika Heyrovského 1203,, 50005, Hradec Králové, Czech Republic. 3. Institute of Organic Chemistry and Biochemistry AS CR, Flemingovo náměstí 2,, 166 10, Praha 6, Czech Republic. 4. Department of Chemistry of Natural Compounds,, University of Chemical Technology, Technická 5, 166 28, 6 - Dejvice, Praha, Czech Republic. 5. Department of Organic Chemistry, Faculty of Science, Charles University, Albertov 6,, 128 43, Praha 2, Czech Republic. 6. Skin Barrier Research Group,, Charles University, Faculty of Pharmacy in Hradec Králové,, Akademika Heyrovského 1203,, 50005, Hradec Králové, Czech Republic. katerina.vavrova@faf.cuni.cz.
Abstract
PURPOSE: To study new skin penetration/permeation enhancers based on amphiphilic galactose derivatives. METHODS: Two series of alkyl and alkenyl galactosides were synthesized and evaluated for their enhancing effect on transdermal/topical delivery of theophylline (TH), hydrocortisone (HC) and cidofovir (CDV), reversibility of their effects on transepidermal water loss (TEWL) and skin impedance, interaction with the stratum corneum using infrared spectroscopy, and cytotoxicity on keratinocytes and fibroblasts. RESULTS: Initial evaluation identified 1-(α-D-galactopyranosyl)-(2E)-pentadec-2-ene A15 as a highly potent enhancer - it increased TH and HC flux through human skin 8.5 and 5 times, respectively. Compound A15 increased the epidermal concentration of a potent antiviral CDV 7 times over that reached by control and Span 20 (an established sugar-based enhancer). Infrared spectroscopy of human stratum corneum indicated interaction of A15 with skin barrier lipids but not proteins. These effects of A15 on the skin barrier were reversible (both TEWL and skin impedance returned to baseline values within 24 h after A15 had been removed from skin). In vitro toxicity of A15 on HaCaT keratinocytes and 3T3 fibroblasts was acceptable, with IC50 values over 60 μM. CONCLUSIONS: Galactosyl pentadecene A15 is a potent enhancer with low toxicity and reversible action.
PURPOSE: To study new skin penetration/permeation enhancers based on amphiphilic galactose derivatives. METHODS: Two series of alkyl and alkenyl galactosides were synthesized and evaluated for their enhancing effect on transdermal/topical delivery of theophylline (TH), hydrocortisone (HC) and cidofovir (CDV), reversibility of their effects on transepidermal water loss (TEWL) and skin impedance, interaction with the stratum corneum using infrared spectroscopy, and cytotoxicity on keratinocytes and fibroblasts. RESULTS: Initial evaluation identified 1-(α-D-galactopyranosyl)-(2E)-pentadec-2-ene A15 as a highly potent enhancer - it increased TH and HC flux through human skin 8.5 and 5 times, respectively. Compound A15 increased the epidermal concentration of a potent antiviral CDV 7 times over that reached by control and Span 20 (an established sugar-based enhancer). Infrared spectroscopy of human stratum corneum indicated interaction of A15 with skin barrier lipids but not proteins. These effects of A15 on the skin barrier were reversible (both TEWL and skin impedance returned to baseline values within 24 h after A15 had been removed from skin). In vitro toxicity of A15 on HaCaT keratinocytes and 3T3 fibroblasts was acceptable, with IC50 values over 60 μM. CONCLUSIONS:Galactosyl pentadeceneA15 is a potent enhancer with low toxicity and reversible action.
Entities:
Keywords:
galactoside; penetration enhancers; sugar; topical drug delivery; transdermal drug delivery
Authors: Monika Kopečná; Miloslav Macháček; Eva Prchalová; Petr Štěpánek; Pavel Drašar; Martin Kotora; Kateřina Vávrová Journal: Pharm Res Date: 2017-01-09 Impact factor: 4.200
Authors: Jakub Novotný; Petra Kovaríková; Michal Novotný; Barbora Janůsová; Alexandr Hrabálek; Katerina Vávrová Journal: Pharm Res Date: 2008-11-14 Impact factor: 4.200
Authors: Anna Nowak; Martyna Zagórska-Dziok; Paula Ossowicz-Rupniewska; Edyta Makuch; Wiktoria Duchnik; Łukasz Kucharski; Urszula Adamiak-Giera; Piotr Prowans; Norbert Czapla; Piotr Bargiel; Jan Petriczko; Marta Markowska; Adam Klimowicz Journal: Molecules Date: 2021-06-07 Impact factor: 4.411