Intranasal administration of edaravone nanoparticles improves its stability and brain bioavailability

TY - JOUR

T1 - Intranasal administration of edaravone nanoparticles improves its stability and brain bioavailability

AU - Lu, Yuan

AU - Wang, Julie Tzu Wen

AU - Li, Na

AU - Zhu, Xiaoqin

AU - Li, Yongjun

AU - Bansal, Sukhi

AU - Wang, Yonglin

AU - Al-Jamal, Khuloud T.

N1 - Publisher Copyright: © 2023 The Authors

PY - 2023/7

Y1 - 2023/7

N2 - 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.

AB - 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.

KW - Amyotrophic lateral sclerosis

KW - Edaravone

KW - Nose-to-brain delivery

KW - PLGA nanoparticles

UR - https://www.scopus.com/pages/publications/85161698079

U2 - 10.1016/j.jconrel.2023.06.001

DO - 10.1016/j.jconrel.2023.06.001

M3 - Article

C2 - 37290723

AN - SCOPUS:85161698079

SN - 0168-3659

VL - 359

SP - 257

EP - 267

JO - Journal of Controlled Release

JF - Journal of Controlled Release

ER -