Pharmacokinetics and antitumor efficacy of paclitaxel-cyclodextrin complexes loaded in mucus-penetrating nanoparticles for oral administration
The authors report a novel approach for enhancing the oral absorption of paclitaxel (PTX) by encapsulation in poly(anhydride) nanoparticles (NPs) containing cyclodextrins and poly(ethylene glycol). Materials & methods: Formulations were prepared using the solvent displacement method. Subsequentl...
| Autores: | , , , , |
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| Tipo de recurso: | artículo |
| Fecha de publicación: | 2014 |
| País: | España |
| Institución: | Universidad de Navarra |
| Repositorio: | Dadun. Depósito Académico Digital de la Universidad de Navarra |
| Idioma: | inglés |
| OAI Identifier: | oai:dadun.unav.edu:10171/37240 |
| Acceso en línea: | https://hdl.handle.net/10171/37240 |
| Access Level: | acceso abierto |
| Palabra clave: | Oral chemotherapy Pharmacokinetics Antitumor efficacy Paclitaxel Poly(anhydride) nanoparticles Cyclodextrins Poly(ethylene glycol) 2000 |
| Sumario: | The authors report a novel approach for enhancing the oral absorption of paclitaxel (PTX) by encapsulation in poly(anhydride) nanoparticles (NPs) containing cyclodextrins and poly(ethylene glycol). Materials & methods: Formulations were prepared using the solvent displacement method. Subsequently, pharmacokinetics and organ distribution assays were evaluated after oral administration into C57BL/6J mice. In addition, antitumor efficacy studies were performed in a subcutaneous tumor model of Lewis lung carcinoma. Results: PTX-loaded NPs displayed sizes between 190–300 nm. Oral NPs achieved drug plasma levels for at least 24 h, with an oral bioavailability of 55–80%. Organ distribution studies revealed that PTX, orally administered in NPs, underwent a similar distribution to intravenous Taxol® (Bristol-Myers-Squibb, NJ, USA). For in vivo antitumor assays, oral strategy maintained a slower tumor growth than intravenous Taxol. Conclusion: PTX orally administered in poly(anhydride) NPs, combined with cyclodextrins and poly(ethylene glycol), displayed sustained plasma levels and significant antitumor effect in a syngenic tumor model of carcinoma in mice. |
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