Enhanced apoptosis and mitochondrial cell death by paclitaxel-loaded TPP-TPGS1000-functionalized nanoemulsion

Background: The present research was designed to develop a nanoemulsion (NE) of triphenylphosphine-D-alpha-tocopheryl-polyethylene glycol succinate (TPP-TPGS(1000)) and paclitaxel (PTX) to effectively deliver PTX to improve breast cancer therapy. Materials & methods: A quality-by-design approach was applied for optimization and in vitro and in vivo characterization were performed. Results: The TPP-TPGS(1000)-PTX-NE enhanced cellular uptake, mitochondrial membrane depolarization and G(2)M cell cycle arrest compared with free-PTX treatment. In addition, pharmacokinetics, biodistribution and in vivo live imaging studies in tumor-bearing mice showed that TPP-TPGS(1000)-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. Conclusion: TPP-TPGS(1000)-PTX-NE improved the efficacy of breast cancer treatment by enhancing its effectiveness and decreasing drug toxicity.

Automated summary

The aim of this study was to develop a nanoemulsion (NE) for the effective delivery of paclitaxel (PTX) in breast cancer therapy. The TPP-TPGS(1000)-PTX-NE showed enhanced cellular uptake, mitochondrial membrane depolarization, and cell cycle arrest compared to free-PTX treatment. In vivo studies in tumor-bearing mice demonstrated superior performance of TPP-TPGS(1000)-PTX-NE in pharmacokinetics, biodistribution, and live imaging, with histological and survival investigations confirming its non-toxicity and potential for breast cancer treatment.