Inclusion complex of novel curcumin analogue CDF and β-cyclodextrin (1:2) and its enhanced in vivo anticancer activity against pancreatic cancer

Pharm Res. 2012 Jul;29(7):1775-86. doi: 10.1007/s11095-012-0700-1. Epub 2012 Feb 10.

Abstract

Purpose: Several formulations have been proposed to improve the systemic delivery of novel cancer therapeutic compounds, including cyclodextrin derivatives. We aimed to synthesize and characterize of CDF-β-cyclodextrin inclusion complex (1:2) (CDFCD).

Methods: The compound was characterized by Fourier transform infrared, differential scanning calorimetry, powder X-ray diffraction studies, H1 & C13 NMR studies and scanning electron microscopic analysis. Its activity was tested against multiple cancer cell lines, and in vivo bioavailability was checked.

Results: CDF-β-cyclodextrin was found to lower IC(50) value by half when tested against multiple cancer cell lines. It preferentially accumulated in the pancreas, where levels of CDF-β-cyclodextrin in mice were 10 times higher than in serum, following intravenous administration of an aqueous CDF-β-cyclodextrin preparation.

Conclusions: Novel curcumin analog CDF preferentially accumulates in the pancreas, leading to its potent anticancer activity against pancreatic cancer cells. Synthesis of such CDF-β-cyclodextrin self-assembly is an effective strategy to enhance its bioavailability and tissue distribution, warranting further evaluation for CDF delivery in clinical settings for treatment of human malignancies.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents / administration & dosage*
  • Antineoplastic Agents / chemistry*
  • Antineoplastic Agents / pharmacokinetics
  • Antineoplastic Agents / pharmacology
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Curcuma / chemistry
  • Curcumin / administration & dosage*
  • Curcumin / analogs & derivatives*
  • Curcumin / pharmacokinetics
  • Curcumin / pharmacology
  • Drug Carriers / chemistry*
  • Female
  • Halogenation
  • Humans
  • Mice
  • Models, Molecular
  • Pancreas / drug effects
  • Pancreas / metabolism
  • Pancreatic Neoplasms / drug therapy*
  • Pancreatic Neoplasms / metabolism
  • Solubility
  • beta-Cyclodextrins / chemistry*

Substances

  • Antineoplastic Agents
  • Drug Carriers
  • beta-Cyclodextrins
  • Curcumin