Ex-vivo absorption study of lysine R-lipoate salt, a new pharmaceutical form of R-ALA

Eur J Pharm Sci. 2018 Jun 15:118:200-207. doi: 10.1016/j.ejps.2018.03.025. Epub 2018 Mar 26.

Abstract

Alpha-lipoic acid (ALA) oral supplements were used in many pathologies associated with increased oxidative stress. Although only R-ALA is considered the biologically active form, R,S-ALA is used in therapeutic applications even showing poor water solubility. The aim of this work was to study the absorption and transport mechanism across the intestinal barrier of new R-ALA stable and water soluble form, consisting in the lysine R-ALA salt, in presence and absence of specific inhibitors of Na+/multivitamin (SMVT) and monocarboxylic acids (MCT). The absorption of a new ALA form was investigated at rat everted sacs in comparison with R-ALA, S-ALA, and R,S-ALA. Results showed that duodenum is the best portion of intestine for ALA forms absorption. The absorption percentage of R-ALA, S-ALA, R,S-ALA, and lysine R-ALA salt was 66%, 43%, 55%, and 70%, respectively. The modest effect of the SMVT inhibitor biotin demonstrated that this transporter system is not principally involved in the absorption of lysine R-lipoate salt across the rat intestinal barrier. On the contrary, the MCT inhibitor octanoic acid significantly reduced the transport of this salt, whit an absorption decrease of R-ALA and lysine R-lipoate salt of 28% and 24%, respectively. Since the highest concentration of these inhibitors did not completely inhibit the absorption of lysine R-lipoate salt, other transport mechanisms probably operate for its intracellular delivery. The new form of ALA, lysine R-lipoate salt, was the most absorbed respect to the other ALA forms demonstrating that this compound is more suitable for oral administration. This new salt could represent a promising candidate for ALA oral supplementation.

Keywords: Everted sac; Intestinal absorption; Lysine R-lipoate salt; R-lipoic acid; Transepithelial transport.

MeSH terms

  • Animals
  • In Vitro Techniques
  • Intestinal Absorption*
  • Lysine / metabolism*
  • Male
  • Permeability
  • Rats, Wistar
  • Thioctic Acid / analogs & derivatives*
  • Thioctic Acid / metabolism*

Substances

  • Thioctic Acid
  • Lysine