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

Area of Science:

• Pharmaceutical Sciences
• Drug Delivery Systems
• Nanotechnology in Medicine

Background:

• Bortezomib (BTZ) is an effective anticancer drug, but its clinical use is restricted by poor aqueous solubility.
• Developing strategies to improve BTZ solubility is crucial for enhancing its therapeutic performance.

Purpose of the Study:

• To engineer a sulfobutylether-β-cyclodextrin (SBE-β-CD) inclusion complex to enhance the solubility and therapeutic efficacy of bortezomib (BTZ).
• To evaluate the in vitro and in vivo performance of the novel BTZ-SBE-β-CD formulation.

Main Methods:

• Aqueous complexation and freeze-drying were used to create the BTZ-SBE-β-CD inclusion complex (F1).
• Phase solubility analysis, differential scanning calorimetry (DSC), and Fourier-transform infrared (FTIR) spectroscopy were employed to characterize the complex.
• In vitro cytotoxicity assays and in vivo antitumor efficacy studies in C26 tumor-bearing mice were conducted.

Main Results:

• The F1 formulation achieved a 25.7-fold increase in BTZ solubility at a 1:20 molar ratio.
• Complex formation was confirmed by DSC and FTIR.
• While in vitro cytotoxicity was slightly reduced, the F1 formulation demonstrated significantly improved in vivo antitumor efficacy (52.14% TGD vs. 29.34% for conventional BTZ).
• A model drug complex (F1') showed enhanced cellular uptake and tumor accumulation.

Conclusions:

• SBE-β-CD serves as a promising platform for encapsulating BTZ, leading to improved solubility and drug delivery.
• The developed BTZ-SBE-β-CD complex exhibits enhanced in vivo anticancer efficacy and warrants further investigation for clinical applications.