Enhanced Apoptosis and Mitochondrial Cell Death by Paclitaxel-Loaded TPP-TPGS ₁₀₀₀ -Functionalized Nanoemulsion

Abstract

<b>Background:</b> The present research was designed to develop a nanoemulsion (NE) of triphenylphosphine-D-α-tocopheryl-polyethylene glycol succinate (TPP-TPGS₁₀₀₀) and paclitaxel (PTX) to effectively deliver PTX to improve breast cancer therapy. <b>Materials & methods:</b> A quality-by-design approach was applied for optimization and <i>in vitro</i> and <i>in vivo</i> characterization were performed. <b>Results:</b> The TPP-TPGS₁₀₀₀-PTX-NE enhanced cellular uptake, mitochondrial membrane depolarization and G₂M cell cycle arrest compared with free-PTX treatment. In addition, pharmacokinetics, biodistribution and <i>in vivo</i> live imaging studies in tumor-bearing mice showed that TPP-TPGS₁₀₀₀-PTX-NE had superior performance compared with free-PTX treatment. Histological and survival investigations ascertained the nontoxicity of the nanoformulation, suggesting new opportunities and potential to treat breast cancer. <b>Conclusion:</b> TPP-TPGS₁₀₀₀-PTX-NE improved the efficacy of breast cancer treatment by enhancing its effectiveness and decreasing drug toxicity.