Nanoparticle Formulations of Antioxidants for the Management of Oxidative Stress in Stroke: A Review

Abstract

Stroke is currently one of the primary causes of morbidity and mortality worldwide. Unfortunately, there has been a lack of effective stroke treatment. Therefore, novel treatment strategies are needed to decrease stroke-induced morbidity and promote the patient’s quality of life. Reactive oxygen species (ROS) have been recognized as one of the major causes of brain injury after ischemic stroke. Antioxidant therapy seems to be an effective treatment in the management of oxidative stress relevant to inflammatory disorders like stroke. However, the in vivo efficacy of traditional anti-oxidative substances is greatly limited due to their non-specific distribution and poor localization in the disease region. In recent years, antioxidant nanoparticles (NPs) have demonstrated a clinical breakthrough for stroke treatment. Some NPs have intrinsic antioxidant properties and act as antioxidants to scavenge ROS. Moreover, NPs provide protection to the antioxidant agents/enzymes while effectively delivering them into unreachable areas like the brain. Because of their nanoscale dimensions, NPs are able to efficiently pass through the BBB, and easily reach the damaged site. Here, we discuss the challenges, recent advances, and perspectives of antioxidant NPs in stroke treatment.

Novel Multi-Antioxidant Approach for Ischemic Stroke Therapy Targeting the Role of Oxidative Stress

“…Additionally, after the restoration of blood flow into the brain, the re-entry of oxygenated blood leads to the “oxygen paradox” phenomenon, accompanied by further ROS production, causing greater damage to neurons, astrocytes, oligodendrocytes, and microglia [ 8 ]. The entire IRI process, therefore, includes OS-mediated damage by enhancing inflammation and via endothelial dysfunction, leading to the disruption of the blood–brain barrier (BBB); microglial activation; lipid peroxidation; and direct cellular death through ferroptosis, pyroptosis, necroptosis, autophagy, and apoptosis, culminating in potential chronic damage, mainly due to glial scar formation, chronic inflammation, impaired axonal regeneration, impaired remyelination, and impaired neo-angiogenesis [ 9 , 10 , 11 , 12 ].…”

Advanced Nano-Drug Delivery Systems in the Treatment of Ischemic Stroke

“…Excessive free radicals cause cellular damage, DNA damage, skeleton disruption, and lipid peroxidation, ultimately resulting in neuronal damage and brain death [70,71]. In particular, the free radical blowout after reperfusion exposes neurons to even more severe challenges [72,73]. In addition, free radicals can stimulate the secretion of cytokines as well as the expression of adhesion molecules, which mediate inflammatory and immune responses, thereby exacerbating a brain tissue reperfusion injury [74].…”