Pharmaceutical Research

, Volume 34, Issue 3, pp 640–653 | Cite as

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

  • Monika Kopečná
  • Miloslav Macháček
  • Eva Prchalová
  • Petr Štěpánek
  • Pavel Drašar
  • Martin Kotora
  • Kateřina Vávrová
Research Paper

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.

KEY WORDS

penetration enhancers sugar topical drug delivery transdermal drug delivery 

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

Supplementary material

11095_2016_2093_MOESM1_ESM.docx (217 kb)
ESM 1(DOCX 216 kb)

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Copyright information

© Springer Science+Business Media New York 2017

Authors and Affiliations

  • Monika Kopečná
    • 1
  • Miloslav Macháček
    • 2
  • Eva Prchalová
    • 3
  • Petr Štěpánek
    • 4
  • Pavel Drašar
    • 4
  • Martin Kotora
    • 3
    • 5
  • Kateřina Vávrová
    • 1
  1. 1.Skin Barrier Research Group, Faculty of Pharmacy in Hradec KrálovéCharles UniversityHradec KrálovéCzech Republic
  2. 2.Department of Biochemical Sciences, Faculty of Pharmacy in Hradec KrálovéCharles UniversityHradec KrálovéCzech Republic
  3. 3.Institute of Organic Chemistry and Biochemistry AS CRPraha 6Czech Republic
  4. 4.Department of Chemistry of Natural CompoundsUniversity of Chemistry and TechnologyPraha 6Czech Republic
  5. 5.Department of Organic Chemistry, Faculty of ScienceCharles University in PraguePraha 2Czech Republic

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