title: The water-soluble inclusion complex of ilexgenin A with β-cyclodextrin polymer--a novel lipid-lowering drug candidate.
abstract: 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.
authors.affiliation: College of Medicine, Yangzhou University, 11 Huaihai Rd, Jiangsu Province, Yangzhou, 225002, Jiangsu, PR China.
authors.forename: Chang
authors.initials: C
authors.lastname: Liu
authors.forename: Wang
authors.initials: W
authors.lastname: Zhang
authors.forename: Qiang
authors.initials: Q
authors.lastname: Wang
authors.forename: Yun
authors.initials: Y
authors.lastname: Sun
authors.forename: Guo-wang
authors.initials: GW
authors.lastname: Diao
mesh_terms: D000818:Animals; D002784:Cholesterol / Q000097:blood; D004195:Disease Models, Animal; D006949:Hyperlipidemias / Q000097:blood / Q000188:drug therapy* / Q000378:metabolism; D000960:Hypolipidemic Agents / Q000097:blood / Q000737:chemistry / Q000494:pharmacology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008968:Molecular Conformation; D011108:Polymers / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D012995:Solubility; D014315:Triterpenes / Q000097:blood / Q000737:chemistry / Q000494:pharmacology*; D014867:Water / Q000737:chemistry; D047392:beta-Cyclodextrins / Q000097:blood / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D000960:Hypolipidemic Agents; D011108:Polymers; D014315:Triterpenes; D047392:beta-Cyclodextrins; C468850:ilexgenin A; D014867:Water; D002784:Cholesterol; C031215:betadex