School of Medicinal Sciences and Health Products, Telemedicine and Telepharmacy Center, University of Camerino, via Madonna delle Carceri 9, 62032 Camerino, Italy.
School of Medicinal Sciences and Health Products, Medicinal Chemistry Unit, University of Camerino, via S. Agostino 1, 62032 Camerino, Italy.
Eur J Pharm Sci. 2018 Jun 15;118:200-207. doi: 10.1016/j.ejps.2018.03.025. Epub 2018 Mar 26.
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.
α-硫辛酸（ALA）口服补充剂已被用于多种与氧化应激增加相关的疾病。尽管只有 R-ALA 被认为具有生物活性，但 R,S-ALA 也被用于治疗应用，尽管其水溶性较差。本工作旨在研究新型 R-ALA 稳定且水溶性形式赖氨酸 R-ALA 盐的肠内屏障吸收和转运机制，该盐的形式存在于 Na/多种维生素（SMVT）和单羧酸（MCT）的特定抑制剂。与 R-ALA、S-ALA 和 R,S-ALA 相比，在大鼠外翻囊中研究了新的 ALA 形式的吸收情况。结果表明，十二指肠是 ALA 形式吸收的最佳肠段。R-ALA、S-ALA、R,S-ALA 和赖氨酸 R-ALA 盐的吸收百分比分别为 66%、43%、55%和 70%。SMVT 抑制剂生物素的适度作用表明，该转运体系统并非主要参与赖氨酸 R-硫辛酸盐通过大鼠肠内屏障的吸收。相反，MCT 抑制剂辛酸显著降低了这种盐的转运，使 R-ALA 和赖氨酸 R-硫辛酸盐的吸收分别减少了 28%和 24%。由于这些抑制剂的最高浓度并未完全抑制赖氨酸 R-硫辛酸盐的吸收，因此可能存在其他转运机制来实现其细胞内传递。新型 ALA 形式赖氨酸 R-硫辛酸盐的吸收量高于其他 ALA 形式，表明该化合物更适合口服给药。这种新盐可能是 ALA 口服补充的有前途的候选物。
