Galactosyl Pentadecene Reversibly Enhances Transdermal and Topical Drug Delivery
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To study new skin penetration/permeation enhancers based on amphiphilic galactose derivatives.
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.
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.
Galactosyl pentadecene A15 is a potent enhancer with low toxicity and reversible action.
Key wordsgalactoside penetration enhancers sugar topical drug delivery transdermal drug delivery
Dulbecco’s modified Eagle’s medium
High performance liquid chromatography
Phosphate buffered saline
Sodium dodecyl sulfate
- Span 20
Transepidermal water loss
Acknowledgments and Disclosures
This work was supported by the Czech Science Foundation (13-23891S). MK was supported by Charles University (88615 and SVV 260401). We thank Iva Vencovská and Lenka Poštová Slavětínská for technical assistance.
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