4.5 Article

The efficacy and neuroprotective effects of edaravone-loaded mPEG-b-PLGA polymeric nanoparticles on human neuroblastoma SH-SY5Y cell line as in vitro model of ischemia

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ELSEVIER
DOI: 10.1016/j.jddst.2022.103378

Keywords

Ischemic stroke; Edaravone; mPEG-b-PLGA micelle; SH-SY5Y cells; Neuroprotection

Funding

  1. Deputy of Research of Zanjan Uni-versity of Medical Sciences [A-10-966-17, ZUMS.REC.1398.0103]

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This study investigated the neuroprotective effects of polymeric micelles loaded with Edaravone in ischemia-induced neuroblastoma cell line. The results showed that the Edaravone-loaded micelles had a significant impact in reducing cell damage and apoptosis compared to free Edaravone.
Stroke is the second leading cause of death and disability worldwide. The present study was designed to investigate the neuroprotective effects of polymeric micelles loaded with Edaravone on ischemia-induced in human neuroblastoma cell line (SH-SY5Y). Polymethoxy ethylene glycol-polylactic-co-glycolic acid (mPEG-bPLGA) was first synthesized, and its physicochemical properties were determined. Micelles were prepared by the nanoprecipitation method. The size of micelles was 155 +/- 2.5 nm with a surface charge of -15 +/- 0.94 and polydispersity index (PDI) of 0.11. The examination of the morphology of micelles performed by transmission electron microscopy (TEM) and atomic force microscopy (AFM) showed that the size of particles was less than 155 +/- 2.5 nm, and the morphology was spherical. The drug loading (DL) was determined about 13 +/- 1.4% and encapsulation efficiency was 65 +/- 0.79%. Drug delivery was analyzed using UV-VIS spectroscopy. The impact of different concentrations of free and micelle-containing Edaravone was performed on SH-SY5Y cells under normal and oxygen and glucose deprivation (OGD) conditions. Lactate dehydrogenase (LDH), nitric oxide (NO) activity, Intracellular reactive oxygen species (ROS) and apoptosis rate were significantly reduced in cells treated with edaravone loaded-micelle in addition to a significant reduction in the expression of pro-apoptotic gene (Bax) and increase in the expression of anti-apoptotic genes (HSP70 and Bcl-2). Consequently, according to the result of the study Edaravone-loaded micelles had a significant rate of neuroprotective effects than free Edaravone against ischemia-induced oxidative damage.

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