Inclusion complexes of noscapine in beta-cyclodextrin offer better solubility and improved pharmacokinetics

Cancer Chemother Pharmacol. 2010 Feb;65(3):537-48. doi: 10.1007/s00280-009-1060-3. Epub 2009 Jul 14.


Purpose: Noscapine (NOS) is a unique class of tubulin-binding anticancer agents. Their potential usefulness as anticancer drugs is however limited by the poor bioavailability, thus necessitating administration of a higher dose regime in the range of 300-600 mg/kg for tumor growth inhibition. To augment bioavailability, we prepared an inclusion complex of NOS in beta-cyclodextrin (beta-CD) and evaluated its physico-chemical characteristics.

Method and results: Our phase-solubility analysis shows a 1:1-complexation (Kc approximately 0.454 mM(-1)) of NOS with beta-CD that offers better dissolution properties. We confirmed complex formation in solid state by differential scanning calorimetry, powder X-ray diffractometry, Fourier-transform infrared spectroscopy, 1H nuclear magnetic resonance spectroscopy, rotating frame Overhauser enhancement spectroscopy and by molecular modeling methods. Based upon theoretical calculations in gas phase, we propose O-CH2-O- in orientation of NOS in the beta-CD cavity. The thermal behavior data also provides complementary evidences of complex formation. The pharmacokinetic studies showed a 1.87-fold increase in bioavailability of NOS upon complexation in the beta-CD inclusion complex state as compared to free NOS. Furthermore, the complex retains the anticancer attributes of NOS.

Conclusion: Our studies propose for the first time a stable NOS-beta-CD inclusion complex as an effective approach to enhance the solubility and bioavailability of NOS for anticancer therapy.

MeSH terms

  • Administration, Oral
  • Animals
  • Area Under Curve
  • Biological Availability
  • Calorimetry, Differential Scanning
  • Cell Line, Tumor
  • Chromatography, High Pressure Liquid
  • Drug Compounding
  • Drug Stability
  • Humans
  • Magnetic Resonance Spectroscopy
  • Male
  • Metabolic Clearance Rate
  • Mice
  • Models, Molecular
  • Molecular Structure
  • Noscapine / administration & dosage
  • Noscapine / chemistry*
  • Noscapine / pharmacokinetics*
  • Solubility
  • Spectroscopy, Fourier Transform Infrared
  • Temperature
  • X-Ray Diffraction
  • beta-Cyclodextrins / chemistry*


  • beta-Cyclodextrins
  • Noscapine
  • betadex