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Intranasal administration of edaravone nanoparticles improves its stability and brain bioavailability.
- Source :
-
Journal of Controlled Release . Jul2023, Vol. 359, p257-267. 11p. - Publication Year :
- 2023
-
Abstract
- The clinical application of EDV, a potent antioxidant drug approved for amyotrophic lateral sclerosis (ALS), is limited by its short biological half-life and poor water solubility necessitating hospitalization during intravenous infusion. Nanotechnology-based drug delivery constitutes a powerful tool through inferring drug stability and targeted drug delivery improving drug bioavailability at the diseased site. Nose-to-brain drug delivery offers direct access to the brain bypassing the blood brain barrier and reducing systemic biodistribution. In this study, we designed EDV-loaded poly(lactic- co -glycolic acid) (PLGA)-based polymeric nanoparticles (NP-EDV) for intranasal administration. NPs were formulated by the nanoprecipitation method. Morphology, EDV loading, physicochemical properties, shelf-life stability, in vitro release and pharmacokinetic assessment in mice were conducted. EDV was efficiently loaded into ∼90 nm NPs, stable up to 30 days of storage, at ∼3% drug loading. NP-EDV reduced H 2 O 2 -induced oxidative stress toxicity in mouse microglial cell line BV-2. Optical imaging and ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) showed that intranasal delivery of NP-EDV offered higher and more sustained brain uptake of EDV compared to intravenous administration. This study is the first of its kind to develop an ALS drug in a nanoparticulate formulation for nose-to-brain delivery raising hope to ALS patients where currently treatment options are limited to two clinically approved drugs only. [Display omitted] [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 01683659
- Volume :
- 359
- Database :
- Academic Search Index
- Journal :
- Journal of Controlled Release
- Publication Type :
- Academic Journal
- Accession number :
- 164866434
- Full Text :
- https://doi.org/10.1016/j.jconrel.2023.06.001