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

Authors
Bernabeu, Ezequiel Adrian; Helguera, Gustavo Fernando; Legaspi, María Julia; Gonzalez, Lorena; Höcht, Christian; Taira, Carlos Alberto; Chiappetta, Diego Andrés
Publication Year
2013
Language
English
Format
article
Status
Published version
Description
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® (UTmethod)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 PTXloaded 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.
Fil: Bernabeu, Ezequiel Adrian. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Tecnología Farmacéutica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Helguera, Gustavo Fernando. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Tecnología Farmacéutica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Legaspi, María Julia. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Tecnología Farmacéutica; Argentina
Fil: Gonzalez, Lorena. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Química Biológica; Argentina
Fil: Höcht, Christian. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Farmacología; Argentina
Fil: Taira, Carlos Alberto. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Farmacología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Chiappetta, Diego Andrés. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Tecnología Farmacéutica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Subject
IN VIVO PHARMACOKINETIC STUDIES
PACLITAXEL
PCL-TPGS
POLYMERIC NANOPARTICLES
POLYMERIC NANOPARTICLES
Nano-materiales
Nanotecnología
INGENIERÍAS Y TECNOLOGÍAS
Nano-materiales
Nanotecnología
INGENIERÍAS Y TECNOLOGÍAS
Access level
Restricted access
License
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repository
CONICET Digital (CONICET)
Institution
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identifier
oai:ri.conicet.gov.ar:11336/26799