title: A water-soluble inclusion complex of pedunculoside with the polymer β-cyclodextrin: a novel anti-inflammation agent with low toxicity.
abstract: More than 50% of new drug candidates in drug discovery are lipophilic and exhibit poor aqueous solubility, which results in poor bioavailability and a lack of dose proportionality. Here, we improved the solubility of pedunculoside (PE) by generating a water-soluble inclusion complex composed of PE and the polymer β-cyclodextrin (CDP). We characterized this novel complex by 1H NMR, FT-IR, UV-vis spectroscopy, powder X-ray diffractometry and thermogravimetric analysis. The ratio of β-cyclodextrin (β-CD) units in CDP to PE was determined to be 2∶1. The KD value of the inclusion complex was determined to be 4.29×10(-3) mol•L(-1). In contrast to the low solubility of PE, the water-solubility of the PE-CDP complex was greatly enhanced. A preclinical toxicological study indicated that PE-CDP was well tolerated for a single administration. Importantly, the anti-inflammation potency of the PE-CDP complex was higher than that of PE. As a result, the formation of inclusion complexes by water-soluble CDP opens up possible aqueous applications of insoluble drug candidates in drug delivery.
authors.affiliation: College of Medicine, Yangzhou University, Yangzhou, Jiangsu, P. R. China.
authors.forename: Chang
authors.initials: C
authors.lastname: Liu
authors.affiliation: College of Chemistry and Chemical Engineering, Yangzhou University, Yangzhou, Jiangsu, P. R. China.
authors.forename: Wang
authors.initials: W
authors.lastname: Zhang
authors.affiliation: College of Medicine, Yangzhou University, Yangzhou, Jiangsu, P. R. China.
authors.forename: Hao
authors.initials: H
authors.lastname: Yang
authors.affiliation: Chinese Medicine Hospital of Yangzhou City, Yangzhou, Jiangsu, P. R. China.
authors.forename: Weidong
authors.initials: W
authors.lastname: Sun
authors.affiliation: College of Chemistry and Chemical Engineering, Yangzhou University, Yangzhou, Jiangsu, P. R. China.
authors.forename: Xiangdong
authors.initials: X
authors.lastname: Gong
authors.affiliation: College of Medicine, Yangzhou University, Yangzhou, Jiangsu, P. R. China.
authors.forename: Junxian
authors.initials: J
authors.lastname: Zhao
authors.affiliation: College of Medicine, Yangzhou University, Yangzhou, Jiangsu, P. R. China.
authors.forename: Yun
authors.initials: Y
authors.lastname: Sun
authors.affiliation: College of Chemistry and Chemical Engineering, Yangzhou University, Yangzhou, Jiangsu, P. R. China.
authors.forename: Guowang
authors.initials: G
authors.lastname: Diao
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000009:adverse effects* / Q000737:chemistry* / Q000627:therapeutic use; D002482:Cellulose / Q000737:chemistry*; D003505:Cyclodextrins / Q000737:chemistry*; D004487:Edema / Q000188:drug therapy; D005947:Glucose / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000737:chemistry / Q000627:therapeutic use; D051379:Mice; D012995:Solubility; D017550:Spectroscopy, Fourier Transform Infrared; D014315:Triterpenes / Q000009:adverse effects* / Q000737:chemistry* / Q000627:therapeutic use; D014867:Water / Q000737:chemistry*
chemical_list: D000893:Anti-Inflammatory Agents; D003505:Cyclodextrins; D014315:Triterpenes; C041953:cyclodextrin polymer; D014867:Water; C084241:pedunculoside; D002482:Cellulose; D005947:Glucose