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.

Hybrid nanoparticles as a new technological approach to enhance the delivery of cholesterol into the brain / Belletti, Daniela; Grabrucker, Andreas Martin; Pederzoli, Francesca; Menerath, Isabel; Vandelli, Maria Angela; Tosi, Giovanni; Duskey, Thomas Jason; Forni, Flavio; Ruozi, Barbara. - In: INTERNATIONAL JOURNAL OF PHARMACEUTICS. - ISSN 0378-5173. - 543:1-2(2018), pp. 300-310. [10.1016/j.ijpharm.2018.03.061]

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

Belletti, Daniela;Pederzoli, Francesca;Vandelli, Maria Angela;Tosi, Giovanni;Duskey, Thomas Jason;Forni, Flavio;Ruozi, Barbara
2018

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.
30-mar-2018
543
1-2
300
310
Hybrid nanoparticles as a new technological approach to enhance the delivery of cholesterol into the brain / Belletti, Daniela; Grabrucker, Andreas Martin; Pederzoli, Francesca; Menerath, Isabel; Vandelli, Maria Angela; Tosi, Giovanni; Duskey, Thomas Jason; Forni, Flavio; Ruozi, Barbara. - In: INTERNATIONAL JOURNAL OF PHARMACEUTICS. - ISSN 0378-5173. - 543:1-2(2018), pp. 300-310. [10.1016/j.ijpharm.2018.03.061]
Belletti, Daniela; Grabrucker, Andreas Martin; Pederzoli, Francesca; Menerath, Isabel; Vandelli, Maria Angela; Tosi, Giovanni; Duskey, Thomas Jason; Forni, Flavio; Ruozi, Barbara
File in questo prodotto:
File Dimensione Formato  
1-s2.0-S0378517318302084-main (2).pdf

non disponibili

Descrizione: Articolo principale
Tipologia: Versione dell'editore (versione pubblicata)
Dimensione 2.17 MB
Formato Adobe PDF
2.17 MB Adobe PDF   Visualizza/Apri   Richiedi una copia
Pubblicazioni consigliate

Caricamento pubblicazioni consigliate

Licenza Creative Commons
I metadati presenti in IRIS UNIMORE sono rilasciati con licenza Creative Commons CC0 1.0 Universal, mentre i file delle pubblicazioni sono rilasciati con licenza Attribuzione 4.0 Internazionale (CC BY 4.0), salvo diversa indicazione.
In caso di violazione di copyright, contattare Supporto Iris

Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/11380/1165838
Citazioni
  • ???jsp.display-item.citation.pmc??? 4
  • Scopus 14
  • ???jsp.display-item.citation.isi??? 14
social impact