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

Abstract

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(ε-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.

• Authors: Ezequiel Bernabeu, Gustavo Helguera, Maria J Legaspi, Lorena Gonzalez, Christian Hocht, Carlos Taira, Diego A Chiappetta
• Journal: Colloids and surfaces. B, Biointerfaces (Colloids Surf B Biointerfaces) Vol. 113 Pg. 43-50 (Jan 01 2014) ISSN: 1873-4367 [Electronic] Netherlands
• PMID: 24060929 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2013 Elsevier B.V. All rights reserved.

Chemical References

• Albumin-Bound Paclitaxel
• Albumins
• Polyesters
• Polymers
• Vitamin E
• polycaprolactone
• Polyethylene Glycols
• tocophersolan
• Paclitaxel

Topics

• Albumin-Bound Paclitaxel
• Albumins (chemistry, pharmacokinetics, pharmacology)
• Animals
• Calorimetry, Differential Scanning
• Cell Line, Tumor
• Cell Proliferation (drug effects)
• Humans
• Male
• Nanoparticles (chemistry)
• Paclitaxel (chemistry, pharmacokinetics, pharmacology)
• Polyesters (chemistry)
• Polyethylene Glycols (chemistry)
• Polymers (chemistry)
• Rats
• Rats, Wistar
• Vitamin E (analogs & derivatives, chemistry)