Paclitaxel-loaded PCL–TPGS nanoparticles: In vitro and in vivo performance compared with Abraxane®

• Paclitaxel-loaded PCL–TPGS nanoparticles were successfully prepared.
• The ultra-sonication method was the more efficient process to obtain nanoparticles.
• Nanoparticles had better anticancer activities than PTX and Abraxane®.
• Nanoparticles presented better pharmacokinetic parameters than Taxol® and Abraxane®.

The purpose of this work was to develop Cremophor® EL-free nanoparticles (NPs) loaded with Paclitaxel (PTX) in order to improve the drug i.v. pharmacokinetic profile and to evaluate its activity against commercially available formulations such as Taxol® and Abraxane®. PTX-loaded poly(ɛ-caprolactone)–alpha tocopheryl polyethylene glycol 1000 succinate (PCL–TPGS) NPs were prepared using three different techniques: (i) by nanoprecipitation (NPr-method), (ii) by emulsion-solvent evaporation homogenized with an Ultra-Turrax® (UT-method) and (iii) by emulsion-solvent evaporation homogenized with an ultrasonicator (US-method). The NPs prepared by US-method showed the smallest size and the highest drug content. The NPs exhibited a slow and continuous release of PTX. The in vitro anti-tumoral activity was assessed using two human breast cancer cell lines (MCF-7 and MDA-MB-231) with the WTS assay. Cytotoxicity studies with both cell lines showed that PTX-loaded PCL–TPGS NPs exhibited better anti-cancer activity compared to PTX solution and the commercial formulation Abraxane® at different concentrations. Importantly, in the case of triple negative MDA-MB-231 breast cancer cells, the IC50 value for PTX-loaded PCL–TPGS NPs was 7.8 times lower than Abraxane®. Finally, in vivo studies demonstrated that PTX-loaded PCL–TPGS NPs exhibited longer systemic circulation time and slower plasma elimination rate than Taxol® and Abraxane®. Therefore, the novel NPs investigated might be an alternative nanotechnological platform for PTX delivery system in cancer chemotherapy.

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