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

International Journal of Molecular Sciences

Ryota Uchida¹  Kosuke Iwamoto¹  Suetada Nagayama¹  Atsushi Miyajima¹  Hinako Okamoto³  Naoko Ikuta²  Hiroshi Fukumi³  Keiji Terao³  Takashi Hirota¹ 

[1] Department of Biopharmaceutics, Faculty of Pharmaceutical Science, Tokyo University of Science, 2641 Yamazaki, Noda-shi, Chiba 278-8510, Japan; E-Mails:;Graduate School of Medicine, Kobe University, 7-5-2 Kusunoki-cho Chuo-ku, Kobe 650-0017, Japan; E-Mail:;CycloChem Bio Co., Ltd., KIBC654R 5-5-2 Minatojima-minamimachi Chuo-ku, Kobe 650-0047, Japan; E-Mails:

关键词: γ-cyclodextrin;    inclusion complex;    R-α-lipoic acid;    pharmacokinetic-profile;    absorption;    intraduodenal administration;    rats;    X-ray imaging;   

DOI  :  10.3390/ijms160510105

来源: mdpi

【 摘 要 】

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.

【 授权许可】

CC BY   
© 2015 by the authors; licensee MDPI, Basel, Switzerland.