title: Natural polymer-stabilized multiple water-in-oil-in-water emulsions: a novel dermal drug delivery system for 5-fluorouracil.
abstract: OBJECTIVE
  The aim of this study was to create multiple water-in-oil-in-water (W/O/W) emulsions with an increased long-term stability as skin delivery systems for the hydrophilic model drug 5-fluorouracil.
  
  
  METHODS
  Multiple W/O/W emulsions were prepared in a one-step emulsification process, and were characterized regarding particle size, microstructure and viscosity. In-vitro studies on porcine skin with Franz-type diffusion cells, tape stripping experiments and attenuated total reflectance-fourier transform infrared spectroscopy (ATR-FTIR) were performed.
  
  
  RESULTS
  The addition of Solagum AX, a natural polymer mixture of acacia and xanthan gum, led to multiple W/O/W emulsions with a remarkably increased long-term stability in comparison to formulations without a thickener. The higher skin diffusion of 5-fluorouracil from the multiple emulsions compared with an O/W-macroemulsion could be explained by ATR-FTIR. Shifts to higher wave numbers and increase of peak areas of the asymmetric and symmetric CH2 stretching vibrations confirmed a transition of parts of the skin lipids from an ordered to a disordered state after impregnation of porcine skin with the multiple emulsions.
  
  
  CONCLUSIONS
  Solagum AX is highly suitable for stabilization of the created multiple emulsions. Moreover, these formulations showed superiority over a simple O/W-macroemulsion regarding skin permeation and penetration of 5-fluorouracil.
authors.affiliation: Research Platform 'Characterisation of Drug Delivery Systems on Skin and Investigations of Involved Mechanisms', University of Vienna, Vienna, Austria.
authors.forename: Magdalena
authors.initials: M
authors.lastname: Hoppel
authors.forename: Denise
authors.initials: D
authors.lastname: Mahrhauser
authors.forename: Christina
authors.initials: C
authors.lastname: Stallinger
authors.forename: Florian
authors.initials: F
authors.lastname: Wagner
authors.forename: Michael
authors.initials: M
authors.lastname: Wirth
authors.forename: Claudia
authors.initials: C
authors.lastname: Valenta
mesh_terms: D000045:Acacia; D000279:Administration, Cutaneous; D000818:Animals; D016503:Drug Delivery Systems; D004355:Drug Stability; D004655:Emulsions / Q000737:chemistry; D005472:Fluorouracil / Q000008:administration & dosage*; D057927:Hydrophobic and Hydrophilic Interactions; D008055:Lipids; D009821:Oils; D010316:Particle Size; D011108:Polymers / Q000737:chemistry; D011135:Polysaccharides, Bacterial; D012867:Skin / Q000378:metabolism*; D017550:Spectroscopy, Fourier Transform Infrared; D013552:Swine; D014783:Viscosity; D014867:Water
chemical_list: D004655:Emulsions; D008055:Lipids; D009821:Oils; D011108:Polymers; D011135:Polysaccharides, Bacterial; D014867:Water; C002563:xanthan gum; D005472:Fluorouracil
keywords: 5-fluorouracil; ATR-FTIR; multiple emulsions; optical light microscopy; skin