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dc.contributor.advisorIrache, J.M. (Juan Manuel)-
dc.contributor.advisorEsparza, I. (Irene)-
dc.creatorPeñalva, R. (Rebeca)-
dc.identifier.citationPEÑALVA SOBRÓN, Rebeca. “Protein nanoparticles for oral delivery of bioactives”. Irache, J. M. y Esparza, I. (dirs.). Tesis doctoral. Universidad de Navarra, Pamplona, 2015.es_ES
dc.description.abstractFood grade proteins can be considered as adequate materials for the preparation of nanoparticles and microparticles. They offer several advantages such as their digestibility, low price and good capability to interact with a wide variety of compounds and nutrients. The aim of this work was to prepare, characterize and evaluate casein and zein nanoparticles for the oral delivery of bioactives. In this order, casein and zein nanoparticles were prepared by a coacervation and desolvation process respectively, followed by purification, concentration and finally dried by spray-drying. The resulting nanoparticles displayed a mean size between 150-300 nm with negative zeta potential. Biodistribution studies in rats showed mucopenetrating abilities for casein nanoparticles and mucus-adhesion properties for zein ones in the proximal jejunum of the rats. Folic acid, resveratrol and quercetin were selected as bioactives and encapsulated into both kind of nanoparticles with encapsulation efficiencies between 50-80%. Casein and zein nanoparticles containing folic acid, resveratrol or quercetin orally administered to male wistar rats displayed in all cases higher drug levels in plasma for at least 24 hours, with longer residence time for zein nanoparticles. This resulted in an increase in the oral bioavailability of the bioactives up to 30-70%. Moreover, the combination of these casein and zein nanoparticles encapsulating quercetin with a P-gP inhibitor, such as 2-hydroxypropyl-b-cyclodextrin (HP-β-CD), was a more effective strategy to increase the oral bioavailability of the active. Besides, the developed zein nanoparticles containing quercetin and resveratrol were evaluated in a LPS endotoxic mice model. Results showed that animals pre-treated with nanoparticles were able to diminish the endotoxic symptoms induced in mice by the intraperitoneal administration of LPS compared to the flavonoids on daily basics. In addition, serum TNF-α also significantly decreased in those animals receiving quercetin encapsulated in zein nanoparticles combined with HP-β-CD. In conclusion, these casein and zein nanocarriers appear to be promising systems for the increase the oral bioavailability of different bioactives.es_ES
dc.subjectPreparación de fármacoses_ES
dc.subjectAcción de los fármacoses_ES
dc.subjectMaterias Investigacion::Farmaciaes_ES
dc.titleProtein nanoparticles for oral delivery of bioactiveses_ES

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