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

Author:

Yadav Pavan K12ORCID,Saklani Ravi12ORCID,Tiwari Amrendra K12ORCID,Verma Saurabh12,Rana Rafquat1ORCID,Chauhan Divya12ORCID,Yadav Pooja12ORCID,Mishra Keerti1ORCID,Kedar Ashwini S1ORCID,Kalleti Navodayam3,Gayen Jiaur R12,Wahajuddin Muhammad1ORCID,Rath Srikanta K3,Mugale Madhav N3,Mitra Kalyan4ORCID,Sharma Deepak1,Chourasia Manish K12ORCID

Affiliation:

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

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

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

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

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.

Funder

Department of Science and Technology, New Delhi, India

Publisher

Future Medicine Ltd

Subject

Development,General Materials Science,Biomedical Engineering,Medicine (miscellaneous),Bioengineering

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