Trehalose-Based Nucleolipids as Nanocarriers for Autophagy Modulation: An In Vitro Study

The Autophagy Lysosomal Pathway is one of the most important mechanisms for removing dysfunctional cellular components. Increasing evidence suggests that alterations in this pathway play a pathogenic role in Parkinson’s disease, making it a point of particular vulnerability. Numerous studies have pr...

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Main Authors: Anthony Cunha, Alexandra Gaubert, Julien Verget, Marie-Laure Thiolat, Philippe Barthélémy, Laurent Latxague, Benjamin Dehay
Format: Article
Language:English
Published: MDPI AG 2022-04-01
Series:Pharmaceutics
Subjects:
Online Access:https://www.mdpi.com/1999-4923/14/4/857
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author Anthony Cunha
Alexandra Gaubert
Julien Verget
Marie-Laure Thiolat
Philippe Barthélémy
Laurent Latxague
Benjamin Dehay
author_facet Anthony Cunha
Alexandra Gaubert
Julien Verget
Marie-Laure Thiolat
Philippe Barthélémy
Laurent Latxague
Benjamin Dehay
author_sort Anthony Cunha
collection DOAJ
description The Autophagy Lysosomal Pathway is one of the most important mechanisms for removing dysfunctional cellular components. Increasing evidence suggests that alterations in this pathway play a pathogenic role in Parkinson’s disease, making it a point of particular vulnerability. Numerous studies have proposed nanotechnologies as a promising approach for delivering active substances within the central nervous system to treat and diagnose neurodegenerative diseases. In this context, the aim was to propose the development of a new pharmaceutical technology for the treatment of neurodegenerative diseases. We designed a trehalose-based nanosystem by combining both a small natural autophagy enhancer molecule named trehalose and an amphiphilic nucleolipid conjugate. To improve nucleolipid protection and cellular uptake, these conjugates were formulated by rapid mixing in either solid lipid nanoparticles (Ø = 120.4 ± 1.4 nm) or incorporated into poly(lactic-co-glycolic acid) nanoparticles (Ø = 167.2 ± 2.4 nm). In vitro biological assays demonstrated a safe and an efficient cellular uptake associated with autophagy induction. Overall, these nucleolipid-based formulations represent a promising new pharmaceutical tool to deliver trehalose and restore the autophagy impaired function.
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spelling doaj.art-99ec7833cca74964a6a1113fe93c20df2023-12-01T21:19:01ZengMDPI AGPharmaceutics1999-49232022-04-0114485710.3390/pharmaceutics14040857Trehalose-Based Nucleolipids as Nanocarriers for Autophagy Modulation: An In Vitro StudyAnthony Cunha0Alexandra Gaubert1Julien Verget2Marie-Laure Thiolat3Philippe Barthélémy4Laurent Latxague5Benjamin Dehay6Univ. Bordeaux, INSERM U1212, CNRS UMR 5320, ARNA, ARN: Régulations Naturelle et Artificielle, ChemBioPharm, 146 rue Léo Saignat, F-33076 Bordeaux, FranceUniv. Bordeaux, INSERM U1212, CNRS UMR 5320, ARNA, ARN: Régulations Naturelle et Artificielle, ChemBioPharm, 146 rue Léo Saignat, F-33076 Bordeaux, FranceUniv. Bordeaux, INSERM U1212, CNRS UMR 5320, ARNA, ARN: Régulations Naturelle et Artificielle, ChemBioPharm, 146 rue Léo Saignat, F-33076 Bordeaux, FranceUniv. Bordeaux, CNRS, IMN, UMR 5293, F-33000 Bordeaux, FranceUniv. Bordeaux, INSERM U1212, CNRS UMR 5320, ARNA, ARN: Régulations Naturelle et Artificielle, ChemBioPharm, 146 rue Léo Saignat, F-33076 Bordeaux, FranceUniv. Bordeaux, INSERM U1212, CNRS UMR 5320, ARNA, ARN: Régulations Naturelle et Artificielle, ChemBioPharm, 146 rue Léo Saignat, F-33076 Bordeaux, FranceUniv. Bordeaux, CNRS, IMN, UMR 5293, F-33000 Bordeaux, FranceThe Autophagy Lysosomal Pathway is one of the most important mechanisms for removing dysfunctional cellular components. Increasing evidence suggests that alterations in this pathway play a pathogenic role in Parkinson’s disease, making it a point of particular vulnerability. Numerous studies have proposed nanotechnologies as a promising approach for delivering active substances within the central nervous system to treat and diagnose neurodegenerative diseases. In this context, the aim was to propose the development of a new pharmaceutical technology for the treatment of neurodegenerative diseases. We designed a trehalose-based nanosystem by combining both a small natural autophagy enhancer molecule named trehalose and an amphiphilic nucleolipid conjugate. To improve nucleolipid protection and cellular uptake, these conjugates were formulated by rapid mixing in either solid lipid nanoparticles (Ø = 120.4 ± 1.4 nm) or incorporated into poly(lactic-co-glycolic acid) nanoparticles (Ø = 167.2 ± 2.4 nm). In vitro biological assays demonstrated a safe and an efficient cellular uptake associated with autophagy induction. Overall, these nucleolipid-based formulations represent a promising new pharmaceutical tool to deliver trehalose and restore the autophagy impaired function.https://www.mdpi.com/1999-4923/14/4/857nucleolipidsnanoparticlesPLGAtrehaloseautophagy
spellingShingle Anthony Cunha
Alexandra Gaubert
Julien Verget
Marie-Laure Thiolat
Philippe Barthélémy
Laurent Latxague
Benjamin Dehay
Trehalose-Based Nucleolipids as Nanocarriers for Autophagy Modulation: An In Vitro Study
Pharmaceutics
nucleolipids
nanoparticles
PLGA
trehalose
autophagy
title Trehalose-Based Nucleolipids as Nanocarriers for Autophagy Modulation: An In Vitro Study
title_full Trehalose-Based Nucleolipids as Nanocarriers for Autophagy Modulation: An In Vitro Study
title_fullStr Trehalose-Based Nucleolipids as Nanocarriers for Autophagy Modulation: An In Vitro Study
title_full_unstemmed Trehalose-Based Nucleolipids as Nanocarriers for Autophagy Modulation: An In Vitro Study
title_short Trehalose-Based Nucleolipids as Nanocarriers for Autophagy Modulation: An In Vitro Study
title_sort trehalose based nucleolipids as nanocarriers for autophagy modulation an in vitro study
topic nucleolipids
nanoparticles
PLGA
trehalose
autophagy
url https://www.mdpi.com/1999-4923/14/4/857
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