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Research Article

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

    Pavan K Yadav

    Division of Pharmaceutics & Pharmacokinetics, CSIR-Central Drug Research Institute, Lucknow, Uttar Pradesh, 226031, India

    Academy of Scientific & Innovative Research (AcSIR), Ghaziabad, 201002, India

    ,
    Ravi Saklani

    Division of Pharmaceutics & Pharmacokinetics, CSIR-Central Drug Research Institute, Lucknow, Uttar Pradesh, 226031, India

    Academy of Scientific & Innovative Research (AcSIR), Ghaziabad, 201002, India

    ,
    Amrendra K Tiwari

    Division of Pharmaceutics & Pharmacokinetics, CSIR-Central Drug Research Institute, Lucknow, Uttar Pradesh, 226031, India

    Academy of Scientific & Innovative Research (AcSIR), Ghaziabad, 201002, India

    ,
    Saurabh Verma

    Division of Pharmaceutics & Pharmacokinetics, CSIR-Central Drug Research Institute, Lucknow, Uttar Pradesh, 226031, India

    Academy of Scientific & Innovative Research (AcSIR), Ghaziabad, 201002, India

    ,
    Rafquat Rana

    Division of Pharmaceutics & Pharmacokinetics, CSIR-Central Drug Research Institute, Lucknow, Uttar Pradesh, 226031, India

    ,
    Divya Chauhan

    Division of Pharmaceutics & Pharmacokinetics, CSIR-Central Drug Research Institute, Lucknow, Uttar Pradesh, 226031, India

    Academy of Scientific & Innovative Research (AcSIR), Ghaziabad, 201002, India

    ,
    Pooja Yadav

    Division of Pharmaceutics & Pharmacokinetics, CSIR-Central Drug Research Institute, Lucknow, Uttar Pradesh, 226031, India

    Academy of Scientific & Innovative Research (AcSIR), Ghaziabad, 201002, India

    ,
    Keerti Mishra

    Division of Pharmaceutics & Pharmacokinetics, CSIR-Central Drug Research Institute, Lucknow, Uttar Pradesh, 226031, India

    ,
    Ashwini S Kedar

    Division of Pharmaceutics & Pharmacokinetics, CSIR-Central Drug Research Institute, Lucknow, Uttar Pradesh, 226031, India

    ,
    Navodayam Kalleti

    Division of Toxicology & Experiment Medicine, CSIR-Central Drug Research Institute, Lucknow, Uttar Pradesh, 226031, India

    ,
    Jiaur R Gayen

    Division of Pharmaceutics & Pharmacokinetics, CSIR-Central Drug Research Institute, Lucknow, Uttar Pradesh, 226031, India

    Academy of Scientific & Innovative Research (AcSIR), Ghaziabad, 201002, India

    ,
    Muhammad Wahajuddin

    Division of Pharmaceutics & Pharmacokinetics, CSIR-Central Drug Research Institute, Lucknow, Uttar Pradesh, 226031, India

    ,
    Srikanta K Rath

    Division of Toxicology & Experiment Medicine, CSIR-Central Drug Research Institute, Lucknow, Uttar Pradesh, 226031, India

    ,
    Madhav N Mugale

    Division of Toxicology & Experiment Medicine, CSIR-Central Drug Research Institute, Lucknow, Uttar Pradesh, 226031, India

    ,
    Kalyan Mitra

    Electron Microscopy Division, Sophisticated Analytical Instrument Facility & Research, CSIR-Central Drug Research Institute, Lucknow, Uttar Pradesh, 226031, India

    ,
    Deepak Sharma

    Division of Pharmaceutics & Pharmacokinetics, CSIR-Central Drug Research Institute, Lucknow, Uttar Pradesh, 226031, India

    &
    Manish K Chourasia

    *Author for correspondence: Tel.: +91 522 277 2450;

    E-mail Address: manish_chourasia@cdri.res.in

    Division of Pharmaceutics & Pharmacokinetics, CSIR-Central Drug Research Institute, Lucknow, Uttar Pradesh, 226031, India

    Academy of Scientific & Innovative Research (AcSIR), Ghaziabad, 201002, India

    Published Online:https://doi.org/10.2217/nnm-2022-0268

    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.

    Graphical abstract

    Papers of special note have been highlighted as: • of interest; •• of considerable interest

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