title: Dodecyl Amino Glucoside Enhances Transdermal and Topical Drug Delivery via Reversible Interaction with Skin Barrier Lipids.
abstract: Skin permeation/penetration enhancers are substances that enable drug delivery through or into the skin.
  
  
  
  To search for new enhancers with high but reversible activity and acceptable toxicity, we synthesized a series of D-glucose derivatives, both hydrophilic and amphiphilic.
  
  
  
  Initial evaluation of the ability of these sugar derivatives to increase permeation and penetration of theophylline through/into human skin compared with a control (no enhancer) or sorbitan monolaurate (Span 20; positive control) revealed dodecyl 6-amino-6-deoxy-α-D-glucopyranoside 5 as a promising enhancer. Furthermore, this amino sugar 5 increased epidermal concentration of a highly hydrophilic antiviral cidofovir by a factor of 7. The effect of compound 5 on skin electrical impedance suggested its direct interaction with the skin barrier. Infrared spectroscopy of isolated stratum corneum revealed no effect of enhancer 5 on the stratum corneum proteins but an overall decrease in the lipid chain order. The enhancer showed acceptable toxicity on HaCaT keratinocyte and 3T3 fibroblast cell lines. Finally, transepidermal water loss returned to baseline values after enhancer 5 had been removed from the skin.
  
  
  
  Compound 5, a dodecyl amino glucoside, is a promising enhancer that acts through a reversible interaction with the stratum corneum lipids.
authors.affiliation: Skin Barrier Research Group, Faculty of Pharmacy in Hradec Králové, Charles University, Akademika Heyrovského 1203, 50005, Hradec Králové, Czech Republic.
authors.forename: Monika
authors.initials: M
authors.lastname: Kopečná
authors.affiliation: Department of Biochemical Sciences, Faculty of Pharmacy in Hradec Králové, Charles University, Akademika Heyrovského 1203, 50005, Hradec Králové, Czech Republic.
authors.forename: Miloslav
authors.initials: M
authors.lastname: Macháček
authors.affiliation: Institute of Organic Chemistry and Biochemistry AS CR, Flemingovo náměstí 2, 166 10, Praha 6, Czech Republic.
authors.forename: Eva
authors.initials: E
authors.lastname: Prchalová
authors.affiliation: Department of Chemistry of Natural Compounds, University of Chemistry and Technology, Technická 5, 166 28, Praha 6, Dejvice, Czech Republic.
authors.forename: Petr
authors.initials: P
authors.lastname: Štěpánek
authors.affiliation: Department of Chemistry of Natural Compounds, University of Chemistry and Technology, Technická 5, 166 28, Praha 6, Dejvice, Czech Republic.
authors.forename: Pavel
authors.initials: P
authors.lastname: Drašar
authors.affiliation: Institute of Organic Chemistry and Biochemistry AS CR, Flemingovo náměstí 2, 166 10, Praha 6, Czech Republic.|Department of Organic Chemistry, Faculty of Science, Charles University in Prague, Hlavova 8, 123 43, Praha 2, Czech Republic.
authors.forename: Martin
authors.initials: M
authors.lastname: Kotora
authors.affiliation: Skin Barrier Research Group, Faculty of Pharmacy in Hradec Králové, Charles University, Akademika Heyrovského 1203, 50005, Hradec Králové, Czech Republic. katerina.vavrova@faf.cuni.cz.
authors.forename: Kateřina
authors.initials: K
authors.lastname: Vávrová
mesh_terms: D000279:Administration, Cutaneous; D000287:Administration, Topical; D000998:Antiviral Agents / Q000008:administration & dosage / Q000378:metabolism; D002460:Cell Line; D002470:Cell Survival; D002626:Chemistry, Pharmaceutical; D000077404:Cidofovir; D003596:Cytosine / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000378:metabolism; D016503:Drug Delivery Systems; D004817:Epidermis / Q000187:drug effects / Q000378:metabolism; D005960:Glucosides / Q000138:chemical synthesis / Q000494:pharmacology*; D006601:Hexoses / Q000494:pharmacology; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D015603:Keratinocytes / Q000187:drug effects / Q000378:metabolism; D008055:Lipids / Q000502:physiology*; D063065:Organophosphonates / Q000008:administration & dosage / Q000378:metabolism; D010539:Permeability; D012867:Skin / Q000187:drug effects* / Q000378:metabolism; D012869:Skin Absorption; D013329:Structure-Activity Relationship; D013806:Theophylline / Q000008:administration & dosage / Q000378:metabolism
chemical_list: D000998:Antiviral Agents; D005960:Glucosides; D006601:Hexoses; D008055:Lipids; D063065:Organophosphonates; C014822:sorbitan monolaurate; D003596:Cytosine; D013806:Theophylline; D000077404:Cidofovir
keywords: penetration enhancers; sugar; topical drug delivery; transdermal drug delivery