Resumen de Oral immunotherapy based on mucus-penetrating nanoparticles against peanut allergy
SUMMARY/RESUMEN The organisation of this thesis is as follows: Chapter 1 comprises a short review pointing the key items of the immunotherapy against allergies and the use of nanocarriers in this field.
Chapter 2 highlights some critical points and partial objectives for consecution of the immunotherapeutic nanocarrier.
Chapter 3 comprises a more extended review describing the mechanisms underlying the natural tolerance to food components and the development of an allergic response in sensitized individuals. Furthermore, the therapeutic approaches that have been proposed to manage these abnormal immunologic responses to a food are also presented and discussed.
Chapter 4 describes the encapsulation process of the peanut extract into poly(anhydride) nanoparticles and its subsequent evaluation on an experimental murine model of peanut allergy. Considering results from this study, a new nanocarrier based on a modification of the initial polymer, in order to reach higher permeation capacity after oral administration, was carried out. Once the modified polymer was prepared it was used to prepare a new batch of nanoparticles and evaluate and test this strategy in order to probe the potential efficacy of the new formulation. This study forms Chapter 5.
Taken into account the different problems faced in previous chapter, Chapter 6 present a new strategy toward an effective oral immunotherapy, in this case, considering a natural polymer (zein) for the preparation of nanoparticles. In this chapter the proteomic profile of the peanut extract used was also performed.
As a combination of what we learn in Chapters 4-6, Chapter 7 and 8 combine the properties of the zein nanoparticles and the targeting of the modified polymer presented in Chapter 5. More in detail the conjugate prepared in Chapter 5 was synthetized by a new method in order to obtain stronger targeting, and therefore, strong capacity to interact with the immune system.
Chapter 9 consists on a general discussion about the results and further research. Finally, Chapter 10 includes final conclusions.
