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2018

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cc-by-nc (c) Silva Abreu, Marcelle et al., 2018
Si us plau utilitzeu sempre aquest identificador per citar o enllaçar aquest document: https://hdl.handle.net/2445/127940

PPARγ agonist-loaded PLGA-PEG nanocarriers as a potencial treatment for Alzheimer's disease: in vitro and in vivo studies.

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Recurs relacionat

https://doi.org/10.2147/IJN.S171490

Resum

Objective: The first aim of this study was to develop a nanocarrier that could transport the peroxisome proliferator-activated receptor agonist, pioglitazone (PGZ) across brain endothelium and examine the mechanism of nanoparticle transcytosis. The second aim was to determine whether these nanocarriers could successfully treat a mouse model of Alzheimer's disease (AD). Methods: PGZ-loaded nanoparticles (PGZ-NPs) were synthesized by the solvent displacement technique, following a factorial design using poly (lactic-co-glycolic acid) polyethylene glycol (PLGA-PEG). The transport of the carriers was assessed in vitro, using a human brain endothelial cell line, cytotoxicity assays, fluorescence-tagged nanocarriers, fluorescence-activated cell sorting, confocal and transmission electron microscopy. The effectiveness of the treatment was assessed in APP/PS1 mice in a behavioral assay and by measuring the cortical deposition of β-amyloid. Results: Incorporation of PGZ into the carriers promoted a 50x greater uptake into brain endothelium compared with the free drug and the carriers showed a delayed release profile of PGZ in vitro. In the doses used, the nanocarriers were not toxic for the endothelial cells, nor did they alter the permeability of the blood-brain barrier model. Electron microscopy indicated that the nanocarriers were transported from the apical to the basal surface of the endothelium by vesicular transcytosis. An efficacy test carried out in APP/PS1 transgenic mice showed a reduction of memory deficit in mice chronically treated with PGZ-NPs. Deposition of β-amyloid in the cerebral cortex, measured by immunohistochemistry and image analysis, was correspondingly reduced. Conclusion: PLGA-PEG nanocarriers cross brain endothelium by transcytosis and can be loaded with a pharmaceutical agent to effectively treat a mouse model of AD.

Matèries

Nanopartícules, Disseny de medicaments, Anàlisi instrumental, Malaltia d'Alzheimer, Ratolins (Animals de laboratori)

Matèries (anglès)

Nanoparticles, Drug design, Instrumental analysis, Alzheimer's disease, Mice (Laboratory animals)

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Col·leccions

Articles publicats en revistes (Farmàcia, Tecnologia Farmacèutica i Fisicoquímica)
Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL))
Articles publicats en revistes (Institut de Nanociència i Nanotecnologia (IN2UB))
Articles publicats en revistes (Patologia i Terapèutica Experimental)

Citació

SILVA ABREU, Marcelle, CALPENA CAMPMANY, Ana cristina, ANDRÉS BENITO, Pol, ASO PÉREZ, Ester, ROMERO, Ignacio a., ROIG-CARLES, David, GROMICOVA, Radka, ESPINA GARCÍA, Marta, FERRER, Isidro (ferrer abizanda), GARCÍA, Maria luisa, MALE, David k.. PPARγ agonist-loaded PLGA-PEG nanocarriers as a potencial treatment for Alzheimer's disease: in vitro and in vivo studies.. _International Journal of Nanomedicine_. 2018. Vol. 13, núm. 5577-5590. [consulta: 23 de gener de 2026]. ISSN: 1176-9114. [Disponible a: https://hdl.handle.net/2445/127940]

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