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 × 10(3) M(-1) and 4.27 × 10(3) 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.