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Author Notes:

Department of Pathology, Emory University School of Medicine, Atlanta, Georgia 30322, United States; Tel: 404-413-5417. Fax: 404-413-5300. E-mail: raneja@gsu.edu

The authors declare no competing financial interest.


Research Funding:

Grants to R.A. (J.M.) from the National Cancer Institute at the National Institutes of Health (1R00CA131489) supported this work in part.

Grants to D.H. from NSF CAREER MCB-0953061 and the Georgia Cancer Coalition also supported this work in part.

National Institutes of Health, United States


  • Science & Technology
  • Life Sciences & Biomedicine
  • Medicine, Research & Experimental
  • Pharmacology & Pharmacy
  • Research & Experimental Medicine
  • Red-Br-Nos
  • colon
  • beta-cyclodextrin (beta-CD)
  • methyl-beta-cyclodextrin (methyl-beta-CD)
  • guar gum microspheres (GGMs)
  • cytotoxicity

Cyclodextrin Complexes of Reduced Bromonoscapine in Guar Gum Microspheres Enhance Colonic Drug Delivery


Journal Title:

Molecular Pharmaceutics


Volume 11, Number 12


, Pages 4339-4349

Type of Work:

Article | Final Publisher PDF


Here, we report improved solubility and enhanced colonic delivery of reduced bromonoscapine (Red-Br-Nos), a cyclic ether brominated analogue of noscapine, upon encapsulation of its cyclodextrin (CD) complexes in bioresponsive guar gum microspheres (GGM). Phase-solubility analysis suggested that Red-Br-Nos complexed with β-CD and methyl-β-CD in a 1:1 stoichiometry, with a stability constant (Kc) of 2.29 × 103 M-1 and 4.27 × 103 M-1. Fourier transforms infrared spectroscopy indicated entrance of an O-CH2 or OCH3-C6H4-OCH3 moiety of Red-Br-Nos in the β-CD or methyl-β-CD cavity. Furthermore, the cage complex of Red-Br-Nos with β-CD and methyl-β-CD was validated by several spectral techniques. Rotating frame Overhauser enhancement spectroscopy revealed that the Ha proton of the OCH3-C6H4-OCH3 moiety was closer to the H5 proton of β-CD and the H3 proton of the methyl-β-CD cavity. The solubility of Red-Br-Nos in phosphate buffer saline (PBS, pH ∼ 7.4) was improved by ∼10.7-fold and ∼21.2-fold when mixed with β-CD and methyl-β-CD, respectively. This increase in solubility led to a favorable decline in the IC50 by ∼2-fold and ∼3-fold for Red-Br-Nos-β-CD-GGM and Red-Br-Nos-methyl-β-CD-GGM formulations respectively, compared to free Red-Br-Nos-β-CD and Red-Br-Nos-methyl-β-CD in human colon HT-29 cells. GGM-bearing drug complex formulations were found to be highly cytotoxic to the HT-29 cell line and further effective with simultaneous continuous release of Red-Br-Nos from microspheres. This is the first study to showing the preparation of drug-complex loaded GGMS for colon delivery of Red-Br-Nos that warrants preclinical assessment for the effective management of colon cancer.

Copyright information:

© 2014 American Chemical Society.

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