| Autor: |
Mursaleen L; School of Life Sciences, University of Westminster, 115 New Cavendish Street, London W1W 6UW, UK.; Department of Pharmaceutics, UCL School of Pharmacy, 29-39 Brunswick Square, London WC1N 1AX, UK.; The Cure Parkinson's Trust, 120 New Cavendish St, Fitzrovia, London W1W 6XX, UK., Noble B; School of Life Sciences, University of Westminster, 115 New Cavendish Street, London W1W 6UW, UK., Chan SHY; Department of Pharmaceutics, UCL School of Pharmacy, 29-39 Brunswick Square, London WC1N 1AX, UK., Somavarapu S; Department of Pharmaceutics, UCL School of Pharmacy, 29-39 Brunswick Square, London WC1N 1AX, UK., Zariwala MG; School of Life Sciences, University of Westminster, 115 New Cavendish Street, London W1W 6UW, UK. |
| Abstrakt: |
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. |
