Preparation of Sorafenib tosylate self-emulsified drug delivery system and the effect on combination therapy with Bosutinib against HCT116/SW1417 cells

Abstract

The Sorafenib tosylate (ST) emulsified drug delivery system (ST-SEDDS) was designed and characterized in response to the poor solubility and bioavailability of ST. ST-SEDDS formed fine emulsions with a mean diameter of 158.3 ± 1.4 nm, a narrow size distribution (PDI 0.257), and a Zeta potential of –22.41 ± 1.2 mV after being diluted with 5% glucose. The cytotoxicity of ST- SEDDS against HCT116 and HCT116/SW1417 cells was comparable to that of free ST, with HCT116/SW1417 cells having a half maximal inhibitory concentration of 175 µg/mL. ST-SEDDS in combination with Bosutinib was used to achieve a satisfactory inhibitory effect on HCT116/SW1417 cells. With a combined index of 0.68, the combination of ST-SEDDS and Bosutinib had a superior synergistic effect. And the combination group's cellular uptake of Bosutinib by HCT116/SW1417 cells was significantly higher than the Bosutinib treatment groups. It meant that ST- SEDDS increased HCT116/SW1417 cells' Bosutinib uptake. Finally, SEDDS was a promising alternative formulation for Sorafenib tosylate (ST). Combining ST-SEDDS and Bosutinib for a synergistic effect appears to be a promising strategy for improving antitumor efficacy against HCT116/SW1417 and other multidrug-resistant tumours.

Keywords

• Sorafenib tosylate (ST)
• Self-emulsified drug delivery system
• Bosutinib
• Combination therapy
• Multidrug resistance