Improving dermal delivery of hyaluronic acid by ionic liquids for attenuating skin dehydration

Int J Biol Macromol. 2020 May 1:150:528-535. doi: 10.1016/j.ijbiomac.2020.02.072. Epub 2020 Feb 10.


The aim of this study is to evaluate the enhanced ability of various choline based ionic liquids (ILs) for dermal delivery of hyaluronic acid (HA). Eight ILs were synthesized via neutralization reactions, which were characterized using Fourier transform infrared spectrometer and proton nuclear magnetic resonance. The enhanced capacity of ILs varied with organic acids. The IL formed by choline and citric acid ([Ch][Cit]) exerted the strongest ability to promote HA penetrating deep into the skin among all ILs. The enhanced ability of [Ch][Cit] were still maintained and even improved after diluted by water although it could be disassociated partially according to electricity. The moisture and transepidermal water loss (TEWL) were employed to evaluate the effect of attenuating skin dehydration. As expected, the IL of choline and malic acid ([Ch][Mala]) and [Ch][Cit] increased moisture and decreased TEWL significantly by improving the penetration of HA into skin. Meanwhile, no irritation was observed on skin of nude mice after treatment by the three ILs which showed optimal enhanced effect. In conclusion, ILs could be high potential biocompatible carriers for facilitating HA dermal delivery to resist skin dehydration for medical or cosmetic uses.

Keywords: Choline; Dermal delivery; Hyaluronic acid; Ionic liquids; Toxicity.

MeSH terms

  • Administration, Cutaneous
  • Animals
  • Dehydration
  • Hyaluronic Acid / administration & dosage*
  • Hyaluronic Acid / chemistry*
  • Hydrophobic and Hydrophilic Interactions
  • Ionic Liquids / chemistry*
  • Mice
  • Molecular Structure
  • Permeability
  • Protective Agents / administration & dosage
  • Protective Agents / chemistry
  • Skin / drug effects*
  • Skin / metabolism*
  • Spectroscopy, Fourier Transform Infrared
  • Swine
  • Water


  • Ionic Liquids
  • Protective Agents
  • Water
  • Hyaluronic Acid