Title

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

Authors

Jitender Madan, Georgia State UniversityFollow
Sushma R. Gundala, Georgia State UniversityFollow
Bharat Baruah, Kennesaw State UniversityFollow
Mulpuri Nagaraju, Georgia State UniversityFollow
Clayton Yates, Tuskegee UniversityFollow
Timothy Turner, Jacksonville State UniversityFollow
Vijay Rangari, Tuskegee UniversityFollow
Donald Hamelberg, Georgia State UniversityFollow
Michelle D. Reid, Emory UniversityFollow
Ritu Aneja, Georgia State UniversityFollow

Document Type

Article

Publication Date

10-2014

Abstract

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.

Comments

This is an open access article published under an ACS AuthorChoice License. Originally Published in:

Mol. Pharmaceutics 2014, 11, 4339−4349. doi: https://dx.doi.org/10.1021/mp500408n

Recommended Citation

Madan J, Gundala SR, Baruah B, et al. Cyclodextrin Complexes of Reduced Bromonoscapine in Guar Gum Microspheres Enhance Colonic Drug Delivery. Molecular Pharmaceutics. 2014;11(12):4339-4349. doi:10.1021/mp500408n.

Creative Commons License

This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License