紫杉醇
药理学
细胞毒性
乳腺癌
生物利用度
癌症
化疗
联合疗法
药代动力学
癌症研究
化学
医学
体外
内科学
生物化学
作者
Pavan Yadav,Ravi Saklani,Amrendra K. Tiwari,Sudhir Kumar Verma,Divya Chauhan,Pooja Yadav,Rafquat Rana,Navodayam Kalleti,Jiaur R. Gayen,Wahajuddin,Srikanta Kumar Rath,Madhav Nilakanth Mugale,Kalyan Mitra,Manish K. Chourasia
标识
DOI:10.1016/j.ijpharm.2023.123209
摘要
The most prevalent clinical option for treating cancer is combination chemotherapy. In combination therapy, assessment and optimization for obtaining a synergistic ratio could be obtained by various preclinical setups. Currently, in vitro optimization is used to get synergistic cytotoxicity while constructing combinations. Herein, we co-encapsulated Paclitaxel (PTX) and Baicalein (BCLN) with TPP-TPGS1000 containing nanoemulsion (TPP-TPGS1000-PTX-BCLN-NE) for breast cancer treatment. The assessment of cytotoxicity of PTX and BCLN at different molar weight ratios provided an optimized synergistic ratio (1:5). Quality by Design (QbD) approach was later applied for the optimization as well as characterization of nanoformulation for its droplet size, zeta potential and drug content. TPP-TPGS1000-PTX-BCLN-NE significantly enhanced cellular ROS, cell cycle arrest, and depolarization of mitochondrial membrane potential in the 4T1 breast cancer cell line compared to other treatments. In the syngeneic 4T1 BALB/c tumor model, TPP-TPGS1000-PTX-BCLN-NE outperformed other nanoformulation treatments. The pharmacokinetic, biodistribution and live imaging studies pivoted TPP-TPGS1000-PTX-BCLN-NE enhanced bioavailability and PTX accumulation at tumor site. Later, histology studies confirmed nanoemulsion non-toxicity, expressing new opportunities and potential to treat breast cancer. These results suggested that current nanoformulation can be a potential therapeutic approach to effectively address breast cancer therapy.
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