Solubilization and stabilization of lipoic acid trisulfide by creation of various β-cyclodextrin clathrates

Biosci Biotechnol Biochem. 2024 May 22;88(6):601-607. doi: 10.1093/bbb/zbae042.

Abstract

Lipoic acid trisulfide, a sulfane sulfur-containing trisulfide of α-lipoic acid, holds promise in pharmaceuticals, yet knowledge gaps persist regarding its synthesis, properties, and stability. Here, we synthesized the lipoic acid trisulfide with a purity exceeding 99% from α-lipoic acid on a gram scale and obtained novel β-cyclodextrin clathrates (84%-95% yield). Differential scanning calorimetry confirmed the inclusion of lipoic acid trisulfide in β-cyclodextrins. The resulting β-cyclodextrin clathrates exhibited significant improvements in water solubility and thermal stability. This pioneering study demonstrated a novel approach to the practical preparation of trisulfide and its β-cyclodextrin clathrates as active ingredients, paving the way for clinical development.

Keywords: lipoic acid trisulfide; sulfane sulfur-containing trisulfide; β-cyclodextrin clathrates.

MeSH terms

  • Calorimetry, Differential Scanning
  • Drug Stability
  • Solubility*
  • Sulfides / chemistry
  • Thioctic Acid* / chemistry
  • Water / chemistry
  • beta-Cyclodextrins* / chemistry