Nanopartículas de poli(anhídrido)maléico como adyuvante en inmunoterapia alergénica
- Autores: Jualiana de Souza Reboucas
- Directores de la Tesis: Carlos Gamazo (dir. tes.), Marta Ferrer Puga (codir. tes.)
- Lectura: En la Universidad de Navarra ( España ) en 2012
- Idioma: español
- Tribunal Calificador de la Tesis: Juan Manuel Irache Garreta (presid.), María Luisa Sanz Larruga (secret.), María Teresa Audicana Berasategui (voc.), Pedro Gamboa Setién (voc.), Fernando Pineda de la Losa (voc.)
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- Resumen
Peanut allergy is responsible by the most severe allergic reactions by anaphylaxis induction. However, there is currently no immunotherapy against this disease. The aim of this work was to evaluate the potential application of poly(anhydride) nanoparticles (NP) in peanut immunotherapy. Thus, poly(anhydride) NP loaded with raw or roasted peanut proteins were developed by the solvent displacement method, with some modifications. Then, the NP formulations were dried by lyophilization or spray-drying and their physico-chemical characteristics were determined. The capacity of these polymeric systems was evaluated after intradermal or oral immunization of C57BL/6 mice with a single dose of the different NP formulations. The adjuvant effect of all NP formulations was demonstrated by a stronger and balanced TH1 (IgG2a) and TH2 (IgG1) specific antibody responses. Furthermore, animals immunized with spray-dried-NP loaded with peanut proteins (raw or roasted) showed higher levels of IgG2a than lyophilized-NP, associated with a lower IgE induction. In addition, we achieved a significant decrease of TH2 cytokines (IL-4, IL-5 and IL-6) and an enhancement of a TH1 cytokine (INF-ã) secretion. Thus, immunization with poly(anhydride) NP leads to a robust pro-TH1 immune response, characterized by a high TH1/TH2 ratio. In conclusion, poly(anhydride) nanoparticles promise as a novel approach to immunotherapy against peanut allergy
