Dodecyl Amino Glucoside Enhances Transdermal and Topical Drug Delivery via Reversible Interaction with Skin Barrier Lipids
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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.
KEY WORDSpenetration enhancers sugar topical drug delivery transdermal drug delivery
Dodecyl ester of 6 (dimethylamino)hexanoic acid
Dulbecco’s modified Eagle’s medium
High performance liquid chromatography
Phosphate buffered saline
Sodium dodecyl sulfate
- Span 20
Transepidermal water loss
- Transkarbam 12
ACKNOWLEDGMENTS AND DISCLOSURES
This work was supported by the Czech Science Foundation (13-23891S). MK was supported by Charles University (1404213 and SVV 206183).