Paclitaxel-loaded TPGS enriched self-emulsifying carrier causes apoptosis by modulating survivin expression and inhibits tumour growth in syngeneic mammary tumours.

Paclitaxel-loaded TPGS enriched self-emulsifying carrier causes apoptosis by modulating survivin expression and inhibits tumour growth in syngeneic mammary tumours. Artif Cells Nanomed Biotechnol. 2018 Oct 04;:1-15 Authors: Meher JG, Dixit S, Pathan DK, Singh Y, Chandasana H, Pawar VK, Sharma M, Bhatta RS, Konwar R, Kesharwani P, Chourasia MK 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. P...
Source: Artificial Cells, Nanomedicine and Biotechnology - Category: Biotechnology Tags: Artif Cells Nanomed Biotechnol Source Type: research