Bortezomib/SBE-β-cyclodextrin inclusion complex for improved anticancer performance: formulation, characterization, and biological evaluation

Bortezomib (BTZ) is a potent anticancer agent whose clinical application is limited by poor aqueous solubility. We engineered a sulfobutylether-β-cyclodextrin (SBE-β-CD) inclusion complex via aqueous complexation and freeze-drying to enhance BTZ solubility and therapeutic performance. Phase solubility analysis demonstrated a 25.7-fold increase in BTZ solubility at a 1:20 molar ratio (F1), in 25 °C. Complex formation was confirmed by differential scanning calorimetry (DSC) and Fourier-transform infrared (FTIR) spectroscopy. The F1 formulation exhibited sustained drug release at physiological pH of 7.4. Although F1 showed slightly reduced in vitro cytotoxicity compared with conventional BTZ (cBTZ) in C26 and U266 cell lines, it significantly improved in vivo antitumor efficacy in C26 tumor-bearing mice, achieving a tumor growth delay (TGD) of 52.14% versus 29.34% for cBTZ. Furthermore, a calcein/SBE-β-CD complex (F1', 1:20 molar ratio, as a fluorescent model drug) demonstrated enhanced cellular uptake and tumor accumulation in C26 tumor-bearing mice. These findings highlight SBE-β-CD as a promising platform for BTZ encapsulation, enabling improved drug delivery and anticancer efficacy and merits further investigation.