Mursaleen, L;
Noble, B;
Chan, SHY;
Somavarapu, S;
Zariwala, MG;
(2020)
N-Acetylcysteine Nanocarriers Protect against Oxidative Stress in a Cellular Model of Parkinson's Disease.
Antioxidants
, 9
(7)
, Article 600. 10.3390/antiox9070600.
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Abstract
Oxidative stress is a key mediator in the development and progression of Parkinson’s disease (PD). The antioxidant N-acetylcysteine (NAC) has generated interest as a disease-modifying therapy for PD but is limited due to poor bioavailability, a short half-life, and limited access to the brain. The aim of this study was to formulate and utilise mitochondria-targeted nanocarriers for delivery of NAC alone and in combination with the iron chelator deferoxamine (DFO), and assess their ability to protect against oxidative stress in a cellular rotenone PD model. Pluronic F68 (P68) and dequalinium (DQA) nanocarriers were prepared by a modified thin-film hydration method. An MTT assay assessed cell viability and iron status was measured using a ferrozine assay and ferritin immunoassay. For oxidative stress, a modified cellular antioxidant activity assay and the thiobarbituric acid-reactive substances assay and mitochondrial hydroxyl assay were utilised. Overall, this study demonstrates, for the first time, successful formulation of NAC and NAC + DFO into P68 + DQA nanocarriers for neuronal delivery. The results indicate that NAC and NAC + DFO nanocarriers have the potential characteristics to access the brain and that 1000 μM P68 + DQA NAC exhibited the strongest ability to protect against reduced cell viability (p = 0.0001), increased iron (p = 0.0033) and oxidative stress (p ≤ 0.0003). These NAC nanocarriers therefore demonstrate significant potential to be transitioned for further preclinical testing for PD.
| Type: | Article |
|---|---|
| Title: | N-Acetylcysteine Nanocarriers Protect against Oxidative Stress in a Cellular Model of Parkinson's Disease |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.3390/antiox9070600 |
| Publisher version: | https://doi.org/10.3390/antiox9070600 |
| Language: | English |
| Additional information: | This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ |
| Keywords: | Science & Technology, Life Sciences & Biomedicine, Biochemistry & Molecular Biology, Chemistry, Medicinal, Food Science & Technology, Pharmacology & Pharmacy, N-acetylcysteine, oxidative stress, Parkinson's disease, neurodegeneration, antioxidant capacity, deferoxamine, iron, BLOOD-BRAIN-BARRIER, ANTIOXIDANT ACTIVITY, FENTON REACTION, IRON, NANOPARTICLES, PATHOGENESIS, CELLS, MPTP, MITOCHONDRIA, FERROPTOSIS |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > UCL School of Pharmacy UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > UCL School of Pharmacy > Pharmaceutics |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10111026 |
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