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.
- MeSH
- alkeny aplikace a dávkování chemie MeSH
- aplikace kožní MeSH
- cytosin aplikace a dávkování analogy a deriváty chemie MeSH
- epidermis metabolismus MeSH
- fibroblasty účinky léků metabolismus MeSH
- galaktosa analogy a deriváty chemie MeSH
- galaktosidy aplikace a dávkování chemie MeSH
- hydrokortison aplikace a dávkování chemie MeSH
- keratinocyty účinky léků metabolismus MeSH
- kožní absorpce účinky léků MeSH
- kůže metabolismus MeSH
- lidé MeSH
- lipidy chemie MeSH
- organofosfonáty aplikace a dávkování chemie MeSH
- permeabilita MeSH
- theofylin aplikace a dávkování chemie MeSH
- uvolňování léčiv MeSH
- voda MeSH
- vztahy mezi strukturou a aktivitou MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
