Journal
ARTIFICIAL CELLS NANOMEDICINE AND BIOTECHNOLOGY
Volume 46, Issue -, Pages S344-S358Publisher
TAYLOR & FRANCIS LTD
DOI: 10.1080/21691401.2018.1492933
Keywords
Paclitaxel; SEDDS; TPGS; breast cancer; apoptosis; survivin
Categories
Funding
- Department of Biotechnology, Government of India
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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 +/- 2.64nm), zeta potential (-21.46 +/- 2.52mV), PDI (0.177 +/- 0.012), drug content (4.97 +/- 0.98mg), entrapment efficiency (98.33 +/- 0.54%) and in vitro drug release (51.03 +/- 2.23% PTX at 72h). PTX-SEDDS exhibited IC50; 1.58 +/- 0.12 mu M and a 52.46-folds higher cell uptake in MDA-MB-231 cells along with cellular and nuclear morphology changes. Significantly higher G(2)M 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. [GRAPHICS] .
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