A water-soluble inclusion complex of pedunculoside with the polymer β-cyclodextrin: a novel anti-inflammation agent with low toxicity

PLoS One. 2014 Jul 11;9(7):e101761. doi: 10.1371/journal.pone.0101761. eCollection 2014.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / adverse effects*
  • Anti-Inflammatory Agents / chemistry*
  • Anti-Inflammatory Agents / therapeutic use
  • Cellulose / chemistry*
  • Cyclodextrins / chemistry*
  • Edema / drug therapy
  • Glucose / adverse effects
  • Glucose / analogs & derivatives*
  • Glucose / chemistry
  • Glucose / therapeutic use
  • Mice
  • Solubility
  • Spectroscopy, Fourier Transform Infrared
  • Triterpenes / adverse effects*
  • Triterpenes / chemistry*
  • Triterpenes / therapeutic use
  • Water / chemistry*

Substances

  • Anti-Inflammatory Agents
  • Cyclodextrins
  • Triterpenes
  • cyclodextrin polymer
  • Water
  • pedunculoside
  • Cellulose
  • Glucose

Grants and funding

This work was largely supported by grants from the National Natural Science Foundation of China (Grant Nos. 21273195), the Project Funded by the Priority Academic Program Development of Jiangsu Higher Education Institutions. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.