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- Publisher Website: 10.1016/j.jconrel.2023.06.001
- Scopus: eid_2-s2.0-85161698079
- PMID: 37290723
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Article: Intranasal administration of edaravone nanoparticles improves its stability and brain bioavailability
Title | Intranasal administration of edaravone nanoparticles improves its stability and brain bioavailability |
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Authors | |
Keywords | Amyotrophic lateral sclerosis Edaravone Nose-to-brain delivery PLGA nanoparticles |
Issue Date | 2023 |
Citation | Journal of Controlled Release, 2023, v. 359, p. 257-267 How to Cite? |
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 H2O2-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. |
Persistent Identifier | http://hdl.handle.net/10722/349920 |
ISSN | 2023 Impact Factor: 10.5 2023 SCImago Journal Rankings: 2.157 |
DC Field | Value | Language |
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dc.contributor.author | Lu, Yuan | - |
dc.contributor.author | Wang, Julie Tzu Wen | - |
dc.contributor.author | Li, Na | - |
dc.contributor.author | Zhu, Xiaoqin | - |
dc.contributor.author | Li, Yongjun | - |
dc.contributor.author | Bansal, Sukhi | - |
dc.contributor.author | Wang, Yonglin | - |
dc.contributor.author | Al-Jamal, Khuloud T. | - |
dc.date.accessioned | 2024-10-17T07:01:51Z | - |
dc.date.available | 2024-10-17T07:01:51Z | - |
dc.date.issued | 2023 | - |
dc.identifier.citation | Journal of Controlled Release, 2023, v. 359, p. 257-267 | - |
dc.identifier.issn | 0168-3659 | - |
dc.identifier.uri | http://hdl.handle.net/10722/349920 | - |
dc.description.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 H2O2-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. | - |
dc.language | eng | - |
dc.relation.ispartof | Journal of Controlled Release | - |
dc.subject | Amyotrophic lateral sclerosis | - |
dc.subject | Edaravone | - |
dc.subject | Nose-to-brain delivery | - |
dc.subject | PLGA nanoparticles | - |
dc.title | Intranasal administration of edaravone nanoparticles improves its stability and brain bioavailability | - |
dc.type | Article | - |
dc.description.nature | link_to_subscribed_fulltext | - |
dc.identifier.doi | 10.1016/j.jconrel.2023.06.001 | - |
dc.identifier.pmid | 37290723 | - |
dc.identifier.scopus | eid_2-s2.0-85161698079 | - |
dc.identifier.volume | 359 | - |
dc.identifier.spage | 257 | - |
dc.identifier.epage | 267 | - |
dc.identifier.eissn | 1873-4995 | - |