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Hybrid nanoparticles as a new technological approach to enhance the delivery of cholesterol into the brain

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dc.contributor.author Belletti, Daniela
dc.contributor.author Grabrucker, Andreas M.
dc.contributor.author Pederzoli, Francesca
dc.contributor.author Menrath, Isabel
dc.contributor.author Vandelli, Maria Angela
dc.contributor.author Tosi, Giovanni
dc.contributor.author Duskey, Thomas Jason
dc.contributor.author Forni, Flavio
dc.contributor.author Ruozi, Barbara
dc.date.accessioned 2018-05-04T13:58:23Z
dc.date.issued 2018
dc.identifier.uri http://hdl.handle.net/10344/6816
dc.description peer-reviewed en_US
dc.description The full text of this article will not be available in ULIR until the embargo expires on the 30/03/2019
dc.description.abstract Restoration of the Chol homeostasis in the Central Nervous System (CNS) could be beneficial for the treatment of Huntington's Disease (HD), a progressive, fatal, adult-onset, neurodegenerative disorder. Unfortunately, Chol is unable to cross the blood-brain barrier (BBB), thus a novel strategy for a targeted delivery of Chol into the brain is highly desired. This article aims to investigate the production of hybrid nanoparticles composed by Chol and PLGA (MIX-NPs) modified with g7 ligand for BBB crossing. We described the impact of ratio between components (Chol and PLGA) and formulation process (nanoprecipitation or single emulsion process) on physico-chemical and structural characteristics, we tested MIX-NPs in vitro using primary hippocampal cell cultures evaluating possible toxicity, uptake, and the ability to influence excitatory synaptic receptors. Our results elucidated that both formulation processes produce MIX-NPs with a Chol content higher that 40%, meaning that Chol is a structural particle component and active compound at the same time. The formulation strategy impacted the architecture and reorganization of components leading to some differences in Chol availability between the two types of g7 MIX-NPs. Our results identified that both kinds of MIX-NPs are efficiently taken up by neurons, able to escape lysosomes and release Chol into the cells resulting in an efficient modification in expression of synaptic receptors that could be beneficial in HD. en_US
dc.language.iso eng en_US
dc.publisher Elsevier en_US
dc.relation.ispartofseries International Journal of Pharmaceutics;543 (1-2), pp. 300-310
dc.relation.uri https://doi.org/10.1016/j.ijpharm.2018.03.061
dc.rights This is the author’s version of a work that was accepted for publication in International Journal of Pharmaceutics. Changes resulting from the publishing process, such as peer review, editing, corrections, structural formatting, and other quality control mechanisms may not be reflected in this document. Changes may have been made to this work since it was submitted for publication. A definitive version was subsequently published in .International Journal of Pharmaceutics, 2018, 543 (1-2), pp. 300-310, en_US
dc.subject nanoparticles en_US
dc.subject cholesterol en_US
dc.subject PLGA en_US
dc.subject blood brain barrier en_US
dc.title Hybrid nanoparticles as a new technological approach to enhance the delivery of cholesterol into the brain en_US
dc.type info:eu-repo/semantics/article en_US
dc.type.supercollection all_ul_research en_US
dc.type.supercollection ul_published_reviewed en_US
dc.date.updated 2018-05-04T11:50:40Z
dc.description.version ACCEPTED
dc.identifier.doi 10.1016/j.ijpharm.2018.03.061
dc.relation.projectid UNIMORE Grant FAR 2016 en_US
dc.relation.projectid Telethon Grant 2017 en_US
dc.date.embargoEndDate 2019-03-30
dc.embargo.terms 2019-03-30 en_US
dc.rights.accessrights info:eu-repo/semantics/embargoedAccess en_US
dc.internal.rssid 2741893
dc.internal.copyrightchecked Yes
dc.identifier.journaltitle International journal of pharmaceutics
dc.description.status peer-reviewed


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