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Title: | Microfluidic formulation of diazoxide-loaded solid lipid nanoparticles as a Novel approach for Friedreich's ataxia treatment |
Authors: | Arduino, I Santoro, A De Santis, S Iacobazzi, RM Lopedota, AA Paradies, E Merla, G Anjomani Virmouni, S Palmieri, L Thomas Marobbio, CM Denora, N |
Keywords: | solid lipid nanoparticles;microfluidics;Friedreich ataxia;blood-brain barrier delivery |
Issue Date: | 3-Jun-2024 |
Publisher: | Elsevier |
Citation: | Arduino, I. et al. (2024) 'Microfluidic formulation of diazoxide-loaded solid lipid nanoparticles as a Novel approach for Friedreich's ataxia treatment', Journal of Drug Delivery Science and Technology, 97, 105837, pp. 1 - 9. doi: 10.1016/j.jddst.2024.105837. |
Abstract: | Friedreich ataxia (FRDA) is a hereditary autosomal recessive disorder characterized by frataxin deficiency, impacting mitochondrial function and causing oxidative damage. Diazoxide (DZX), a vasodilating drug used in the management of systemic hypertension, has shown promise in preclinical models but faces challenges in crossing the blood-brain barrier and potential toxicity at higher doses. This study aimed to create solid lipid nanoparticles (SLNs) loaded with DZX by microfluidic technique to improve blood-brain barrier (BBB) penetration and reduce side effects. Employing an in vitro BBB model, SLN-DZX demonstrated enhanced permeability compared to plain DZX. Cell viability assays carried out on FRDA fibroblast cells indicated enhanced viability with 1 μM SLN-DZX. Cellular uptake studies confirmed SLN internalization in FRDA fibroblasts, and subsequent treatment with SLN-DZX significantly reduced both total and mitochondrial ROS levels compared to control and empty SLN-treated cells. These findings suggest SLN-DZX as a potential therapeutic approach for FRDA, mitigating oxidative stress with improved BBB penetration and reduced toxicity. |
Description: | Data availability: Data will be made available on request. |
URI: | https://bura.brunel.ac.uk/handle/2438/29135 |
DOI: | https://doi.org/10.1016/j.jddst.2024.105837 |
ISSN: | 1773-2247 |
Other Identifiers: | ORCiD: Antonella Santoro https://orcid.org/0000-0002-6193-2050 ORCiD: Eleonora Paradies https://orcid.org/0000-0002-1668-7148 ORCiD: Sara Anjomani Virmouni https://orcid.org/0000-0001-5831-780X ORCiD: Nunzio Denora https://orcid.org/0000-0002-7756-7828 105837 |
Appears in Collections: | Dept of Life Sciences Research Papers |
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FullText.pdf | Copyright © 2024 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY license (https://creativecommons.org/licenses/by/4.0/). | 3.01 MB | Adobe PDF | View/Open |
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