Pharmaceutical Research

, Volume 34, Issue 10, pp 2097–2108 | Cite as

Galactosyl Pentadecene Reversibly Enhances Transdermal and Topical Drug Delivery

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

Abstract

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.

Key words

galactoside penetration enhancers sugar topical drug delivery transdermal drug delivery 

Abbreviations

CDV

Cidofovir

DMEM

Dulbecco’s modified Eagle’s medium

ER

Enhancement ratio

HC

Hydrocortisone

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

Supplementary material

11095_2017_2214_MOESM1_ESM.pdf (620 kb)
Supplementary Material. Details of the synthetic procedures and characterization of the prepared compounds. (PDF 619 kb)

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Copyright information

© Springer Science+Business Media, LLC 2017

Authors and Affiliations

  1. 1.Skin Barrier Research Group,Charles University, Faculty of Pharmacy in Hradec Králové,Hradec KrálovéCzech Republic
  2. 2.Department of Biochemical Sciences,Charles University Faculty of Pharmacy in Hradec Králové,Hradec KrálovéCzech Republic
  3. 3.Institute of Organic Chemistry and Biochemistry AS CRPraha 6Czech Republic
  4. 4.Department of Chemistry of Natural Compounds,University of Chemical TechnologyPrahaCzech Republic
  5. 5.Department of Organic Chemistry, Faculty of ScienceCharles UniversityPraha 2Czech Republic

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