Hyaluronic acid lipoate: synthesis and physicochemical properties

Carbohydr Polym. 2013 Mar 1;93(1):273-8. doi: 10.1016/j.carbpol.2012.04.009. Epub 2012 Apr 12.


The synthesis and physicochemical characterisation of mixed lipoic and formic esters of hyaluronan (Lipohyal) are presented in this paper. The synthesis was conducted by activating lipoic acid with 1,1'-carbonyldiimidazole to obtain lipoyl imidazolide, which reacted with hyaluronan (HA) in formamide under basic conditions. This procedure allows researchers to modulate easily the degree of substitution over a range of 0.05-1.8. Radical scavenger properties were analysed by UV-vis spectroscopy, where improved performance was demonstrated for Lipohyal with respect to the HA row material and lipoic acid. The chemical modification also causes HA to show an improved resistance to hyaluronidase digestion. These findings show that Lipohyal is a highly interesting derivative for applications in the tricological and dermo-cosmetic field and as an anti-aging ingredient. Moreover, Lipohyal can be easily crosslinked by UV irradiation, resulting in an innovative hydrogel with distinctive viscoelastic properties that is suitable as both a dermal-filler and as an intra-articular medical device.

MeSH terms

  • Animals
  • Biocatalysis
  • Chemical Phenomena*
  • Cross-Linking Reagents
  • Formamides / chemistry
  • Free Radical Scavengers / chemistry
  • Hyaluronic Acid / analogs & derivatives*
  • Hyaluronic Acid / chemistry
  • Hyaluronic Acid / physiology
  • Hyaluronoglucosaminidase / chemistry
  • Hydrogel, Polyethylene Glycol Dimethacrylate / chemistry
  • Imidazoles / chemistry
  • Spectroscopy, Fourier Transform Infrared
  • Thioctic Acid / analogs & derivatives
  • Thioctic Acid / chemistry*
  • Ultraviolet Rays
  • Viscosity


  • Cross-Linking Reagents
  • Formamides
  • Free Radical Scavengers
  • Imidazoles
  • Hydrogel, Polyethylene Glycol Dimethacrylate
  • formamide
  • N,N-carbonyldiimidazole
  • Thioctic Acid
  • Hyaluronic Acid
  • Hyaluronoglucosaminidase