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...
Main Authors: | , , , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
MDPI AG
2022-04-01
|
Series: | Pharmaceutics |
Subjects: | |
Online Access: | https://www.mdpi.com/1999-4923/14/4/857 |
_version_ | 1827619523734274048 |
---|---|
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. |
first_indexed | 2024-03-09T10:30:18Z |
format | Article |
id | doaj.art-99ec7833cca74964a6a1113fe93c20df |
institution | Directory Open Access Journal |
issn | 1999-4923 |
language | English |
last_indexed | 2024-03-09T10:30:18Z |
publishDate | 2022-04-01 |
publisher | MDPI AG |
record_format | Article |
series | Pharmaceutics |
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 |
work_keys_str_mv | AT anthonycunha trehalosebasednucleolipidsasnanocarriersforautophagymodulationaninvitrostudy AT alexandragaubert trehalosebasednucleolipidsasnanocarriersforautophagymodulationaninvitrostudy AT julienverget trehalosebasednucleolipidsasnanocarriersforautophagymodulationaninvitrostudy AT marielaurethiolat trehalosebasednucleolipidsasnanocarriersforautophagymodulationaninvitrostudy AT philippebarthelemy trehalosebasednucleolipidsasnanocarriersforautophagymodulationaninvitrostudy AT laurentlatxague trehalosebasednucleolipidsasnanocarriersforautophagymodulationaninvitrostudy AT benjamindehay trehalosebasednucleolipidsasnanocarriersforautophagymodulationaninvitrostudy |