Effect of γ-Cyclodextrin Inclusion Complex on the Absorption of R-α-Lipoic Acid in Rats

• Published in: International journal of molecular sciences Vol. 16; no. 5; pp. 10105 - 10120
• Main Authors: Uchida, Ryota, Iwamoto, Kosuke, Nagayama, Suetada, Miyajima, Atsushi, Okamoto, Hinako, Ikuta, Naoko, Fukumi, Hiroshi, Terao, Keiji, Hirota, Takashi
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI 04-05-2015; MDPI AG
• Subjects: absorption; Administration, Oral; Animals; gamma-Cyclodextrins - administration & dosage; gamma-Cyclodextrins - pharmacology; inclusion complex; Intestinal Absorption - drug effects; Intestine, Small - drug effects; Intestine, Small - metabolism; intraduodenal administration; Male; pharmacokinetic-profile; R-α-lipoic acid; Rats; Rats, Sprague-Dawley; Thioctic Acid - administration & dosage; Thioctic Acid - metabolism; X-ray imaging; γ-cyclodextrin
• ISSN: 1422-0067; 1422-0067
• DOI: 10.3390/ijms160510105

R-α-lipoic acid (RLA) is an endogenous organic acid, and works as a cofactor for mitochondrial enzymes and as a kind of antioxidant. Inclusion complexes of RLA with α-, β- or γ-cyclodextrins (CD) were prepared and orally administered as a suspension to rats. Among them, RLA/γ-CD showed the highest plasma exposure, and its area under the plasma concentration-time curve (AUC) of RLA was 2.2 times higher than that after oral administration of non-inclusion RLA. On the other hand, the AUC after oral administration of non-inclusion RLA and RLA/γ-CD to pylorus-ligated rats did not differ. However, the AUC after intraduodenal administration of RLA/γ-CD was 5.1 times higher than that of non-inclusion RLA, and was almost comparable to the AUC after intraduodenal administration of RLA-Na solution. Furthermore, the AUC after intraduodenal administration of RLA/γ-CD was not affected by biliary ligation or co-administration of an amylase inhibitor. These findings demonstrated that RLA was absorbed from the small intestine effectively when orally administered as a γ-CD inclusion complex, which could be easily dissolved in the lumen of the intestine. In conclusion, γ-CD inclusion complex is an appropriate formulation for supplying RLA as a drug or nutritional supplement with respect to absorption.