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• W2894954022 abstract "Paclitaxel (PTX) in its commercial products exhibits adverse effects owing to excipients and also has poor oral bioavailability. Present work is directed towards development of tocopheryl polyethylene glycol succinate-assisted self-nanoemulsifying system (SEDDS) for oral delivery of PTX. Box–Behnken design of experiment was employed to optimize PTX-SEDDS and was characterized for droplet size (29.76 ± 2.64 nm), zeta potential (–21.46 ± 2.52 mV), PDI (0.177 ± 0.012), drug content (4.97 ± 0.98 mg), entrapment efficiency (98.33 ± 0.54%) and in vitro drug release (51.03 ± 2.23% PTX at 72 h). PTX-SEDDS exhibited IC50; 1.58 ± 0.12 µM and a 52.46-folds higher cell uptake in MDA-MB-231 cells along with cellular and nuclear morphology changes. Significantly higher G2M cell cycle arrest, apoptosis, mitochondrial membrane potential disruption and ROS production was exhibited by PTX-SEDDS in comparison to Taxol. Up-regulation of Bax, p21, cleaved-caspase 3, -caspase 9 and down-regulation of Bcl2 and survivin suggested apoptosis via intrinsic pathways. Pharmacokinetic study showed approximately 4-folds higher oral bioavailability of PTX-SEDDS than Taxol. Significant reduction in tumour volume and weight was observed in syngeneic mammary tumour in SD rats. Tumour histopathology and TUNEL assay showed apoptosis in tumour tissue. PTX-SEDDS caused low lung metastasis, and was safe and stable. Conclusively, PTX-SEDDS could be suitable option for oral delivery of PTX." @default.
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• W2894954022 date "2018-10-04" @default.
• W2894954022 modified "2023-09-27" @default.
• W2894954022 title "Paclitaxel-loaded TPGS enriched self-emulsifying carrier causes apoptosis by modulating survivin expression and inhibits tumour growth in syngeneic mammary tumours" @default.
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• W2894954022 doi "https://doi.org/10.1080/21691401.2018.1492933" @default.
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