Paclitaxel-loaded PCL–TPGS nanoparticles: In vitro and in vivo performance compared with 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(ε-caprolactone)...
| Autores: | , , , , , , |
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| Tipo de recurso: | artículo |
| Estado: | Versión publicada |
| Fecha de publicación: | 2013 |
| País: | Argentina |
| Institución: | Consejo Nacional de Investigaciones Científicas y Técnicas |
| Repositorio: | CONICET Digital (CONICET) |
| Idioma: | inglés |
| OAI Identifier: | oai:ri.conicet.gov.ar:11336/26799 |
| Acceso en línea: | http://hdl.handle.net/11336/26799 |
| Access Level: | acceso abierto |
| Palabra clave: | In Vivo Pharmacokinetic Studies Paclitaxel Pcl-Tpgs Polymeric Nanoparticles https://purl.org/becyt/ford/2.10 https://purl.org/becyt/ford/2 |
| Sumario: | 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. |
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