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Dodecyl Amino Glucoside Enhances Transdermal and Topical Drug Delivery via Reversible Interaction with Skin Barrier Lipids

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Abstract

Purpose

Skin permeation/penetration enhancers are substances that enable drug delivery through or into the skin.

Methods

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.

Results

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.

Conclusions

Compound 5, a dodecyl amino glucoside, is a promising enhancer that acts through a reversible interaction with the stratum corneum lipids.

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Abbreviations

CDV:

Cidofovir

DDAK:

Dodecyl ester of 6 (dimethylamino)hexanoic acid

DMEM:

Dulbecco’s modified Eagle’s medium

ER:

Enhancement ratio

HPLC:

High performance liquid chromatography

MTT:

3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide

NR:

Neutral red

PBS:

Phosphate buffered saline

PG:

Propylene glycol

SC:

Stratum corneum

SDS:

Sodium dodecyl sulfate

Span 20:

Sorbitan monolaurate

TEWL:

Transepidermal water loss

TH:

Theophylline

Transkarbam 12:

5-(dodecyloxycarbonyl)pentylammonium 5-(dodecyloxycarbonyl)pentylcarbamate

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ACKNOWLEDGMENTS AND DISCLOSURES

This work was supported by the Czech Science Foundation (13-23891S). MK was supported by Charles University (1404213 and SVV 206183).

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Authors and Affiliations

  1. Skin Barrier Research Group, Faculty of Pharmacy in Hradec Králové, Charles University, Akademika Heyrovského 1203, 50005, Hradec Králové, Czech Republic

    Monika Kopečná & Kateřina Vávrová

  2. Department of Biochemical Sciences, Faculty of Pharmacy in Hradec Králové, Charles University, Akademika Heyrovského 1203, 50005, Hradec Králové, Czech Republic

    Miloslav Macháček

  3. Institute of Organic Chemistry and Biochemistry AS CR, Flemingovo náměstí 2, 166 10, Praha 6, Czech Republic

    Eva Prchalová & Martin Kotora

  4. Department of Chemistry of Natural Compounds, University of Chemistry and Technology, Technická 5, 166 28, Praha 6, Dejvice, Czech Republic

    Petr Štěpánek & Pavel Drašar

  5. Department of Organic Chemistry, Faculty of Science, Charles University in Prague, Hlavova 8, 123 43, Praha 2, Czech Republic

    Martin Kotora

Authors
  1. Monika Kopečná
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Correspondence to Kateřina Vávrová.

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Kopečná, M., Macháček, M., Prchalová, E. et al. Dodecyl Amino Glucoside Enhances Transdermal and Topical Drug Delivery via Reversible Interaction with Skin Barrier Lipids. Pharm Res 34, 640–653 (2017). https://doi.org/10.1007/s11095-016-2093-z

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  • DOI: https://doi.org/10.1007/s11095-016-2093-z

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