51 research outputs found

    Interaction of PLGA Nanoparticles with human plasma proteins

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    Trabajo presentado en Latest Advances on Nanomaterials for Biomedical Application (NANOBIOAPP 2015), celebrado en Barcelona entre el 21 y el 23 de septiembre de 2015Peer reviewe

    Interaction of PLGA Nanoparticles with human plasma proteins

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    Trabajo presentado en el VII Workshop CBN 2015, 7ª Jornada del Departamento de Nanotecnología Química y Biomolecular del IQAC, celebrado en Barcelona el 15 de octubre de 2015

    Behavioral asymmetries and recovery in rats with different degrees of unilateral striatal dopamine depletion

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    A detailed behavioral analysis during the first postoperative week was performed in rats which had sustained various degrees of unilateral neostriatal dopamine (DA) lesions by administration of the neurotoxin 6-hydroxydopamine into the substantia nigra. These animals were assigned to different groups according to their residual DA levels in the damaged neostriatum (as percentage of the intact side). On the first day after toxin injection into the substantia nigra, turning asymmetries (tight turns) toward the side of the lesion were observed in animals with a mean residual DA level of 32% or less. Out of these, the strongest asymmetries were observed in animals with a mean residual DA of 3%. After one week, the asymmetry in tight turns had totally recovered except in those groups with mean residual DA levels of 17% or less. Partial recovery was found in animals with mean residual DA of 9 and 17%, whereas no indication for recovery was found in animals with the most severe lesions (mean residual DA 3%). Measurement of thigmotactic scanning also revealed an asymmetry for the side of the lesion on the first post-operative day. This asymmetry was observed over a wider range of DA lesion than that observed in turning, namely up to a mean residual DA level of 78%. Furthermore, recovery to symmetry was observed in all lesion-groups except in those with more severe lesions (mean residual DA 17% or less). In contrast to turning, the strongest asymmetries were not displayed by the animals with the most severe lesions. Furthermore, locomotor activity was affected by the lesion, since on the first postoperative day locomotion was reduced in animals with mean residual DA of 39% or less. On day 7, this lesion-dependent deficit had recovered to control levels. Finally, the analysis of net turns allowed the prediction of lesion size in animals with residual DA levels of less than 15%. These results are discussed with respect to mechanisms of recovery, the role of lesion size, and the value of different behavioral measures to predict the degree of DAergic lesion.Deutsche Forschungsgemeinschaft/[Hu 306/13-1]/DFG/AlemaniaUCR::Vicerrectoría de Docencia::Salud::Facultad de Medicina::Escuela de MedicinaUCR::Vicerrectoría de Investigación::Unidades de Investigación::Ciencias de la Salud::Centro de Investigación en Neurociencias (CIN

    Galantamine-loaded PLGA nanoparticles, from nano-emulsion templating, as novel advanced drug delivery systems to treat neurodegenerative diseases

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    Polymeric nanoparticles could be promising drug delivery systems to treat neurodegenerative diseases. Among the various methods of nanoparticle preparation, nano-emulsion templating was used in the present study to prepare galantamine-loaded nano-emulsions by a low-energy emulsification method followed by solvent evaporation to obtain galantamine-loaded polymeric nanoparticles. This approach was found to be suitable because biocompatible, biodegradable and safe nanoparticles with appropriate features (hydrodynamic radii around 20 nm, negative surface charge and stability higher than 3 months) for their intravenous administration were obtained. Encapsulation efficiencies higher than 90 wt% were obtained with a sustained drug release profile as compared to that from aqueous and micellar solutions. The enzymatic activity of the drug was maintained at 80% after its encapsulation into nanoparticles that were non-cytotoxic at the required therapeutic concentration. Therefore, novel galantamine-loaded polymeric nanoparticles have been designed for the first time using the nano-emulsification approach and showed the appropriate features to become advanced drug delivery systems to treat neurodegenerative diseases.Financial support from MINECO (grant CTQ2011-29336-CO3-O1), Generalitat de Catalunya (grant 2009-SGR-961) and CIBER-BBN (financed by the Instituto de Salud Carlos III) is acknowledged. Cristina Fornaguera is grateful to AGAUR for their Pre-doctoral Fellowship (grant FI-DGR 2012).Peer reviewe

    PLGA nanoparticles prepared by nano-emulsion templating using low-energy methods as efficient nanocarriers for drug delivery across the blood-brain barrier

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    Neurodegenerative diseases have an increased prevalence and incidence nowadays, mainly due to aging of the population. In addition, current treatments lack efficacy, mostly due to the presence of the blood-brain barrier (BBB) that limits the penetration of the drugs to the central nervous system. Therefore, novel drug delivery systems are required. Polymeric nanoparticles have been reported to be appropriate for this purpose. Specifically, the use of poly-(lactic-co-glycolic acid) (PLGA) seems to be advantageous due to its biocompatibility and biodegradability that ensure safe therapies. In this work, a novel approximation to develop loperamide-loaded nanoparticles is presented: their preparation by nano-emulsion templating using a low-energy method (the phase inversion composition, PIC, method). This nano-emulsification approach is a simple and very versatile technology, which allows a precise size control and it can be performed at mild process conditions. Drug-loaded PLGA nanoparticles were obtained using safe components by solvent evaporation of template nano-emulsions. Characterization of PLGA nanoparticles was performed, together with the study of the BBB crossing. The in vivo results of measuring the analgesic effect using the hot-plate test evidenced that the designed PLGA loperamide-loaded nanoparticles are able to efficiently cross the BBB, with high crossing efficiencies when their surface is functionalized with an active targeting moiety (a monoclonal antibody against the transferrin receptor). These results, together with the nanoparticle characterization performed here are expected to provide sufficient evidences to end up to clinical trials in the near future.Financial support from MINECO (grants CTQ2011-29336-CO3-O1); Generalitat de Catalunya (grant 2009-SGR-961), and CIBER-BBN are acknowledged. CIBER-BBN is an initiative funded by the VI National R&D&I Plan 2008–2011, IniciativaIngenio 2010, Consolider Program, CIBER Actions and financed by the Instituto de Salud Carlos III with assistance from the European Regional Development Fund. Cristina Fornaguera is grateful to AGAUR for their Predoctoral Fellowship (grant FI-DGR 2012).Peer reviewe
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