The Effect of Surfactant on Paclitaxel Nanocrystals: An In Vitro and In Vivo Study
In this study, we first investigated the change of the morphology of paclitaxel (PTX) nanocrystals by varying the type of stabilizer and increasing the amount of D-α-tocopheryl polyethylene glycol 1000 succinate (TPGS) in PTX/TPGS nanocrystals. Rod-shaped nanocrystals changed into relatively thermally stable spherical micelles as the amount of TPGS increased to 1/20 (PTX/TPGS). With these increasing amounts of TPGS, higher cytotoxicity and cellular uptake were observed in P-glycoprotein-overexpressing PTX-resistant (H460/TaxR) cancer cells. Compared to Taxol, PTX/Pluronic F127 (F127) (1/5) nanocrystals, PTX/TPGS (1/5) nanocrystals and PTX/TPGS (1/40) micelles showed significantly sustained in vitro release profiles. Pharmacokinetic studies showed that PTX from these nanoformulations was cleared more rapidly than PTX from Taxol after intravenous administration. However, although presenting an unfavorable pharmacokinetic profile, the biodistribution study showed that PTX/TPGS (1/40) micelles were more effective in promoting accumulation of PTX in drug resistant tumors than Taxol, due to the P-gp inhibition effect of TPGS.
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Document Type: Research Article
Publication date: January 1, 2016
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