Enhanced Apoptosis and Mitochondrial Cell Death by Paclitaxel-Loaded TPP-TPGS <sub>1000</sub> -Functionalized Nanoemulsion
Pavan Kumar Yadav, Ravi Saklani, Amrendra Tiwari, Saurabh Verma, Rafquat Rana, Divya Chauhan, Pooja Yadav, Keerti Mishra, Ashwini Kedar, Navodayam Kalleti, Jiaur R. Gayen, Muhammad Wahajuddin, Srikanta Kumar Rath, Madhav Nilakanth Mugale, Kalyan Mitra, Deepak Sharma, Manish K. Chourasia
Abstract
Background: 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. Materials & methods: A quality-by-design approach was applied for optimization and in vitro and in vivo characterization were performed. Results: 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 in vivo 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. Conclusion: TPP-TPGS1000-PTX-NE improved the efficacy of breast cancer treatment by enhancing its effectiveness and decreasing drug toxicity.