Nanosystems for the oral administration of alkyl-lysophospholipid anti-tumor agents: Development of lipid nanotransporters and preclinical studies
- Autores: Ander Estella Hermoso de Mendoza
- Directores de la Tesis: María José Blanco Prieto (dir. tes.)
- Lectura: En la Universidad de Navarra ( España ) en 2011
- Idioma: inglés
- Número de páginas: 316
- Tribunal Calificador de la Tesis: Paolo Caliceti (presid.), María Dolores Odero de Dios (secret.), Miriam Royo Expósito (voc.), Dolores Torres López (voc.), Pilar Calvo Salde (voc.)
- Materias:
- Enlaces
- Tesis en acceso abierto en: Dadun
- Resumen
Edelfosine is a synthetic alkyl ether phospholipid that represents a promising class of antitumor agents, with limited side effects but presenting a low oral bioavailability. In order to solve this drawback, edelfosine has been entrapped into lipid nanoparticles (LN). The nanosystems have been prepared by the Hot Homogenization technique, which does not require the use of organic solvents, thus reducing toxicity issues. The developed LN had a size of 100 nm, suitable for oral administration, with an encapsulation efficiency up to 90 %. The LN orally administered to mice were mainly absorbed through the lymphatic system and increased by 1500 % the oral bioavailability of the drug. Besides, these nanoparticles significantly increased the drug concentration in the brain due to the inhibition of the blood brain barrier P-glycoprotein. The developed LN were tested against mantle cell lymphoma and glioma xenograft animal models. Mice were treated orally with a solution of edelfosine and with edelfosine loaded LN. Results showed that edelfosine loaded LN were significantly more effective than the oral solution of the drug in both tumor models. Moreover, no metastases were observed in mice treated with the LN, while the edelfosine solution was not able to eliminate the metastatization process. In conclusion, these LN appear to be promising systems for the future therapy of cancer.
