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1.
J Anat ; 232(4): 699-715, 2018 04.
Artículo en Inglés | MEDLINE | ID: mdl-29315537

RESUMEN

Its high metabolic rate and high polyunsaturated fatty acid content make the brain very sensitive to oxidative damage. In the brain, neuronal metabolism occurs at a very high rate and generates considerable amounts of reactive oxygen species and free radicals, which accumulate inside neurons, leading to altered cellular homeostasis and integrity and eventually irreversible damage and cell death. A misbalance in redox metabolism and the subsequent neurodegeneration increase throughout the course of normal aging, leading to several age-related changes in learning and memory as well as motor functions. The neuroprotective function of antioxidants is crucial to maintain good brain homeostasis and adequate neuronal functions. Vitamins E and C are two important antioxidants that are taken up by brain cells via the specific carriers αTTP and SVCT2, respectively. The aim of this study was to use immunohistochemistry to determine the distribution pattern of these vitamin transporters in the brain in a mouse model that shows fewer signs of brain aging and a higher resistance to oxidative damage. Both carriers were distributed widely throughout the entire brain in a pattern that remained similar in 4-, 12-, 18- and 24-month-old mice. In general, αTTP and SVCT2 were located in the same regions, but they seemed to have complementary distribution patterns. Double-labeled cell bodies were detected only in the inferior colliculus, entorhinal cortex, dorsal subiculum, and several cortical areas. In addition, the presence of αTTP and SVCT2 in neurons was analyzed using double immunohistochemistry for NeuN and the results showed that αTTP but not SVCT2 was present in Bergmann's glia. The presence of these transporters in brain regions implicated in learning, memory and motor control provides an anatomical basis that may explain the higher resistance of this animal model to brain oxidative stress, which is associated with better motor performance and learning abilities in old age.


Asunto(s)
Envejecimiento/metabolismo , Encéfalo/metabolismo , Proteínas Portadoras/metabolismo , Estrés Oxidativo , Transportadores de Sodio Acoplados a la Vitamina C/metabolismo , Animales , Antígenos Nucleares/metabolismo , Antioxidantes/metabolismo , Ácido Ascórbico/metabolismo , Biomarcadores/metabolismo , Encéfalo/diagnóstico por imagen , Proteína Ácida Fibrilar de la Glía/metabolismo , Inmunohistoquímica/métodos , Aprendizaje , Masculino , Memoria , Ratones , Ratones Endogámicos BALB C , Ratones Endogámicos C57BL , Ratones Noqueados , Proteínas del Tejido Nervioso/metabolismo , Neuroglía/metabolismo , Neuroglía/ultraestructura , Neuronas/metabolismo , Neuronas/ultraestructura , Vitamina E/metabolismo
2.
Langmuir ; 33(17): 4269-4279, 2017 05 02.
Artículo en Inglés | MEDLINE | ID: mdl-28391698

RESUMEN

Since the past decade, there has been growing interest to grant nanoparticles with diffusion properties across mucosae. In this sense, the nonionic block copolymer Pluronic F127 (PF127) has emerged as a promising coating agent to formulate mucus-penetrating particles. In the journey to find efficient coating agents, researchers have focused more on the effect of the coating agent architecture rather than on the role of the physicochemical properties of the nanoparticle used as the substrate. The current knowledge about mucodiffusive particles is in general based on model-like nanoparticles, such as polystyrene or poly(lactic-co-glycolic) acid nanoparticles, but there is a lack of information about the potential of PF127 on other colloidal systems. This work aims to shed some light on this issue by selecting three oils, palm (solid), coconut (semisolid), and wheat germ (liquid), with different physicochemical properties to formulate PF127-coated nanoemulsions. The obtained nanoemulsions were characterized, and their colloidal stability was tested. Their diffusion capacity was determined by particle tracking after challenging the nanoemulsions across an intestinal porcine mucus layer. In accordance with the evidence of model-like nanoparticles, our results state that PF127 allows mucodiffusion, but its effectiveness as a coating agent clearly depends on the physicochemical properties of the nanostructure core over which PF127 is placed. Among other physicochemical properties, the results certainly showed that the hydrophobic character of the nanostructure core emerges as a critical factor in the formulation of successful PF127 coatings.


Asunto(s)
Emulsiones/química , Excipientes/química , Nanopartículas/química , Poloxámero/química , Tensoactivos/química , Administración Oral , Animales , Aceite de Coco/química , Difusión , Estabilidad de Medicamentos , Concentración de Iones de Hidrógeno , Interacciones Hidrofóbicas e Hidrofílicas , Moco/química , Aceite de Palma/química , Pancreatina/química , Tamaño de la Partícula , Pepsina A/química , Aceites de Plantas/química , Porcinos , alfa-Tocoferol/química
3.
Int J Pharm ; 490(1-2): 209-18, 2015 Jul 25.
Artículo en Inglés | MEDLINE | ID: mdl-25997659

RESUMEN

Most frequently the use of bioactive molecules for the supplementation of food and beverages is hampered by stability limitations or inadequate intestinal absorption. This work evaluates in vitro the role that the interface of the nanoemulsion has on the physicochemical properties, the stability behavior and the enzymatic degradation after oral intake. For that purpose three soybean oil (SB) formulations were studied. These formulations were based on the emulsifier lecithin but modified with two non-ionic surfactants Pluronic(®) F68 (PF68) or Pluronic(®) F127 (PF127) yielding (i) SB-NE (only lecithin on the interface), (ii) SB-NE PF68 (lecithin plus PF68) and 9 (iii) SB-NE PF127 (lecithin plus PF127). All the formulations tested were low polydispersed and showed a size of about 200 nm and ζ-potential of -50 mV. The in vitro colloidal stability assay showed that lecithin itself was able to promote that formulations reach unaltered to the small intestine and facilitate the absorption of the antioxidant payload on a tunable fashion there (with in vitro bioaccessibility values from around 40% up to a 70%). PF68 was able to sterically stabilize the formulation against the aggregation induced by the pH and electrolytes of the simulated gastrointestinal track; however, this surfactant was easily displaced by the lipases of the simulated intestinal milieu being unable to modulate the digestion pattern of the oil droplets in the small intestine. Finally, PF127 displayed a strong steric potential that dramatically reduced the interaction of the oil droplets with lipases in vitro, which will compromise the capacity of the formulation to improve the bioaccessibility of the loaded antioxidant.


Asunto(s)
Antioxidantes/química , Emulsiones/química , Nanopartículas/química , Fármacos Neuroprotectores/química , Disponibilidad Biológica , Química Farmacéutica/métodos , Portadores de Fármacos/química , Emulsionantes/química , Lecitinas/química , Tamaño de la Partícula , Aceite de Soja/química
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