The water-soluble inclusion complex of ilexgenin A with β-cyclodextrin polymer--a novel lipid-lowering drug candidate

• Published in: Organic & biomolecular chemistry Vol. 11; no. 30; p. 4993
• Main Authors: Liu, Chang, Zhang, Wang, Wang, Qiang, Sun, Yun, Diao, Guo-wang
• Format: Journal Article
• Language: English
• Published: England 14-08-2013
• Subjects: Animals; beta-Cyclodextrins - blood; beta-Cyclodextrins - chemistry; beta-Cyclodextrins - pharmacology; Cholesterol - blood; Disease Models, Animal; Hyperlipidemias - blood; Hyperlipidemias - drug therapy; Hyperlipidemias - metabolism; Hypolipidemic Agents - blood; Hypolipidemic Agents - chemistry; Hypolipidemic Agents - pharmacology; Mice; Mice, Inbred C57BL; Molecular Conformation; Polymers - administration & dosage; Polymers - chemistry; Polymers - pharmacology; Solubility; Triterpenes - blood; Triterpenes - chemistry; Triterpenes - pharmacology; Water - chemistry
• ISSN: 1477-0539
• DOI: 10.1039/c3ob40715b

A new water-soluble inclusion complex of ilexgenin A (IGA) with β-cyclodextrin polymer (CDP) was prepared by a facile strategy and characterized by (1)H NMR , FT-IR, and UV-vis spectroscopy. Compared with IGA and the inclusion complex of IGA with β-cyclodextrin (IGA-CD), the solubility of IGA-β-cyclodextrin polymer (IGA-CDP) was greatly enhanced due to the water-soluble CDP host. The ratio of β-cyclodextrin (β-CD) units in CDP to IGA was determined as 2 : 1. KD of the inclusion complex was evaluated as 2.6 × 10(-3) mol L(-1). The effects of IGA-CDP on a hyperlipidemia mouse model were studied by intragastric administration. After 4 weeks, the IGA-CDP treatment resulted in decreased serum levels of total cholesterol and low-density lipoprotein-cholesterol. The effects of IGA-CDP on serum apolipoprotein levels were similar to its effects on lipid levels. By comparing liver area, the effects of IGA-CDP on pre-existing lesions were assessed. Furthermore, the efficacy and potency of water-soluble inclusion complex of IGA-CDP was 2-3 times higher than that of IGA. Taken together, it was possible to develop it to a novel drug candidate to regulate lipid abnormality.