Potent Therapeutic Efficacy of 9-Bromo-Noscapine Against Breast Cancer Cells Via Enhanced Bioavailability of the Noscapine-Cyclodextrin Inclusion Complex.

The poor bioavailability and low therapeutic indices of conventional cancer therapeutics hinder their efficacy despite their promising anticancer potential. This study presents an improved solubility and enhanced drug delivery system against breast cancer by complexing Bromo-Noscapine (9-Br-Nos) with Methyl-β-cyclodextrin (Mβ-CD). After synthesizing the inclusion complex, it was characterized using ultraviolet-visible (UV-Vis) spectroscopy, proton nuclear magnetic resonance (H NMR), Fourier-transform infrared (FT-IR) spectroscopy, X-ray diffraction (XRD), scanning electron microscopy (SEM), and thermogravimetric analysis (TGA). In addition, the arrangement of the drug molecule within the Mβ-CD cavity was confirmed by molecular docking and molecular dynamic simulation. The drug release profile, bioavailability, and anticancer activity of the complex were also evaluated in vitro. Moreover, the toxicity and metabolic clearance kinetics were assessed in vivo using animal model. Furthermore, to explore the molecular mechanism of the anticancer activity of the 9-Br-Nos-Mβ-CD inclusion complex FITC-annexin V apoptosis and western blot analysis were performed to explore the enhanced apoptotic cell death and the modulation of cancer-related proteins in breast cancer cells. In summary, this report demonstrated that the Noscapine-Cyclodextrin inclusion complex enhances the anticancer potential of 9-Br-Nos by modulating its bioavailability and persistence in breast cancer cells.