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Targeting Brain Disease in MPSII: Preclinical Evaluation of IDS-Loaded PLGA Nanoparticles

Mucopolysaccharidosis type II (MPSII) is a lysosomal storage disorder due to the deficit of the enzyme iduronate 2-sulfatase (IDS), which leads to the accumulation of glycosaminoglycans in most organ-systems, including the brain, and resulting in neurological involvement in about two-thirds of the p...

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Autores principales: Rigon, Laura, Salvalaio, Marika, Pederzoli, Francesca, Legnini, Elisa, Duskey, Jason Thomas, D’Avanzo, Francesca, De Filippis, Concetta, Ruozi, Barbara, Marin, Oriano, Vandelli, Maria Angela, Ottonelli, Ilaria, Scarpa, Maurizio, Tosi, Giovanni, Tomanin, Rosella
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6514713/
https://www.ncbi.nlm.nih.gov/pubmed/31022913
http://dx.doi.org/10.3390/ijms20082014
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author Rigon, Laura
Salvalaio, Marika
Pederzoli, Francesca
Legnini, Elisa
Duskey, Jason Thomas
D’Avanzo, Francesca
De Filippis, Concetta
Ruozi, Barbara
Marin, Oriano
Vandelli, Maria Angela
Ottonelli, Ilaria
Scarpa, Maurizio
Tosi, Giovanni
Tomanin, Rosella
author_facet Rigon, Laura
Salvalaio, Marika
Pederzoli, Francesca
Legnini, Elisa
Duskey, Jason Thomas
D’Avanzo, Francesca
De Filippis, Concetta
Ruozi, Barbara
Marin, Oriano
Vandelli, Maria Angela
Ottonelli, Ilaria
Scarpa, Maurizio
Tosi, Giovanni
Tomanin, Rosella
author_sort Rigon, Laura
collection PubMed
description Mucopolysaccharidosis type II (MPSII) is a lysosomal storage disorder due to the deficit of the enzyme iduronate 2-sulfatase (IDS), which leads to the accumulation of glycosaminoglycans in most organ-systems, including the brain, and resulting in neurological involvement in about two-thirds of the patients. The main treatment is represented by a weekly infusion of the functional enzyme, which cannot cross the blood-brain barrier and reach the central nervous system. In this study, a tailored nanomedicine approach based on brain-targeted polymeric nanoparticles (g7-NPs), loaded with the therapeutic enzyme, was exploited. Fibroblasts from MPSII patients were treated for 7 days with NPs loaded with the IDS enzyme; an induced IDS activity like the one detected in healthy cells was measured, together with a reduction of GAG content to non-pathological levels. An in vivo short-term study in MPSII mice was performed by weekly administration of g7-NPs-IDS. Biochemical, histological, and immunohistochemical evaluations of liver and brain were performed. The 6-weeks treatment produced a significant reduction of GAG deposits in liver and brain tissues, as well as a reduction of some neurological and inflammatory markers (i.e., LAMP2, CD68, GFAP), highlighting a general improvement of the brain pathology. The g7-NPs-IDS approach allowed a brain-targeted enzyme replacement therapy. Based on these positive results, the future aim will be to optimize NP formulation further to gain a higher efficacy of the proposed approach.
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spelling pubmed-65147132019-05-30 Targeting Brain Disease in MPSII: Preclinical Evaluation of IDS-Loaded PLGA Nanoparticles Rigon, Laura Salvalaio, Marika Pederzoli, Francesca Legnini, Elisa Duskey, Jason Thomas D’Avanzo, Francesca De Filippis, Concetta Ruozi, Barbara Marin, Oriano Vandelli, Maria Angela Ottonelli, Ilaria Scarpa, Maurizio Tosi, Giovanni Tomanin, Rosella Int J Mol Sci Article Mucopolysaccharidosis type II (MPSII) is a lysosomal storage disorder due to the deficit of the enzyme iduronate 2-sulfatase (IDS), which leads to the accumulation of glycosaminoglycans in most organ-systems, including the brain, and resulting in neurological involvement in about two-thirds of the patients. The main treatment is represented by a weekly infusion of the functional enzyme, which cannot cross the blood-brain barrier and reach the central nervous system. In this study, a tailored nanomedicine approach based on brain-targeted polymeric nanoparticles (g7-NPs), loaded with the therapeutic enzyme, was exploited. Fibroblasts from MPSII patients were treated for 7 days with NPs loaded with the IDS enzyme; an induced IDS activity like the one detected in healthy cells was measured, together with a reduction of GAG content to non-pathological levels. An in vivo short-term study in MPSII mice was performed by weekly administration of g7-NPs-IDS. Biochemical, histological, and immunohistochemical evaluations of liver and brain were performed. The 6-weeks treatment produced a significant reduction of GAG deposits in liver and brain tissues, as well as a reduction of some neurological and inflammatory markers (i.e., LAMP2, CD68, GFAP), highlighting a general improvement of the brain pathology. The g7-NPs-IDS approach allowed a brain-targeted enzyme replacement therapy. Based on these positive results, the future aim will be to optimize NP formulation further to gain a higher efficacy of the proposed approach. MDPI 2019-04-24 /pmc/articles/PMC6514713/ /pubmed/31022913 http://dx.doi.org/10.3390/ijms20082014 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Rigon, Laura
Salvalaio, Marika
Pederzoli, Francesca
Legnini, Elisa
Duskey, Jason Thomas
D’Avanzo, Francesca
De Filippis, Concetta
Ruozi, Barbara
Marin, Oriano
Vandelli, Maria Angela
Ottonelli, Ilaria
Scarpa, Maurizio
Tosi, Giovanni
Tomanin, Rosella
Targeting Brain Disease in MPSII: Preclinical Evaluation of IDS-Loaded PLGA Nanoparticles
title Targeting Brain Disease in MPSII: Preclinical Evaluation of IDS-Loaded PLGA Nanoparticles
title_full Targeting Brain Disease in MPSII: Preclinical Evaluation of IDS-Loaded PLGA Nanoparticles
title_fullStr Targeting Brain Disease in MPSII: Preclinical Evaluation of IDS-Loaded PLGA Nanoparticles
title_full_unstemmed Targeting Brain Disease in MPSII: Preclinical Evaluation of IDS-Loaded PLGA Nanoparticles
title_short Targeting Brain Disease in MPSII: Preclinical Evaluation of IDS-Loaded PLGA Nanoparticles
title_sort targeting brain disease in mpsii: preclinical evaluation of ids-loaded plga nanoparticles
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6514713/
https://www.ncbi.nlm.nih.gov/pubmed/31022913
http://dx.doi.org/10.3390/ijms20082014
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