Toxicity evaluation of poly(anhydride) nanoparticles designed for oral drug delivery
- Autores: Tamara Iglesias Alonso
- Directores de la Tesis: Adela López de Cerain Salsamendi (dir. tes.), Amaya Azqueta Oscoz (codir. tes.)
- Lectura: En la Universidad de Navarra ( España ) en 2016
- Idioma: español
- Número de páginas: 273
- Tribunal Calificador de la Tesis: Ricardo Marcos Dauder (presid.), Ariane Vettorazzi Armental (secret.), Boris Turk (voc.), Pilar Vinardell Martínez-Hidalgo (voc.), Juan Manuel Irache Garreta (voc.)
- Programa de doctorado: Programa de Doctorado en Medicamentos y Salud por la Universidad de Navarra
- Materias:
- Enlaces
- Tesis en acceso abierto en: Dadun
- Resumen
In the last years, the development of nanomaterials has significantly increased due to the immense variety of potential applications in technological sectors. Focusing on the nanocarriers for oral drug delivery, poly(anhydride) nanoparticles (NPs) have received extensive attention due to their unique properties, such as their capability to develop intense adhesive interactions within the intestinal mucosa, their modifiable surface and their biodegradable and easy-to-produce profile. However, current knowledge of the possible adverse health effects is still exceedingly limited.
The aim of this work was to evaluate the in vitro and in vivo toxicity, focusing in genotoxicity, and the in vitro mucus permeability capacity, of poly(anhydride) NPs designed for oral drug delivery. For this purpose, Gantrez® AN 119 NPs combined with 7 hydrophilic ligands were used.
Results showed that, in general, coated NPs exhibit better mucus permeability than the bare ones, being those coated with mannosamine the most permeable ones. Gantrez® AN 119-based NPs did not affect cell metabolism, membrane integrity or viability of Caco-2 cells at the different conditions tested. Moreover, they did not induce a relevant level of DNA strand breaks or oxidized bases neither in Caco-2 nor in L5178Y TK+/- mouse lymphoma cells. In addition, Gantrez ® AN 119 NPs coated with mannosamine, did not induce mutations in L5178Y TK+/- mouse lymphoma cells in an assay performed following the OECD guideline 490. However, they induced DNA strand breaks and oxidized bases in duodenum tissue of mice exposed to 2000 mg/kg bw for 2 and 4 h, in an assay performed following the OECD guideline 489. This effect was not observed at lower doses (500 and 1000 mg/kg bw) or in other tissues along the gastrointestinal tract.
Taking into account all the aforementioned, the present research has established an optimal and safety profile of Gantrez ® AN 119 NPs coated with mannosamine for oral administration of drugs favouring their candidature for their use in medicine. Nevertheless, more studies are needed to complete the toxicological profile of these NPs.
