ABSTRACT
Stroke, a severe medical condition arising from abnormalities in the coagulation-fibrinolysis cycle and metabolic processes, results in brain cell impairment and injury due to blood flow obstruction within the brain. Prompt and efficient therapeutic approaches are imperative to control and preserve brain functions. Conventional stroke medications, including fibrinolytic agents, play a crucial role in facilitating reperfusion to the ischemic brain. However, their clinical efficacy is hampered by short plasma half-lives, limited brain tissue distribution attributed to the blood-brain barrier (BBB), and lack of targeted drug delivery to the ischemic region. To address these challenges, diverse nanomedicine strategies, such as vesicular systems, polymeric nanoparticles, dendrimers, exosomes, inorganic nanoparticles, and biomimetic nanoparticles, have emerged. These platforms enhance drug pharmacokinetics by facilitating targeted drug accumulation at the ischemic site. By leveraging nanocarriers, engineered drug delivery systems hold the potential to overcome challenges associated with conventional stroke medications. This comprehensive review explores the pathophysiological mechanism underlying stroke and BBB disruption in stroke. Additionally, this review investigates the utilization of nanocarriers for current therapeutic and diagnostic interventions in stroke management. By addressing these aspects, the review aims to provide insight into potential strategies for improving stroke treatment and diagnosis through a nanomedicine approach.
ABSTRACT
Stroke accounts for one of the top leading reasons for neurological mortality and morbidity around the globe. Both ischemic and hemorrhagic strokes lead to local hypoxia and are brought about by the occlusion or rupturing of the blood vessels. The events taking place after the onset of a stroke include membrane ion pump failure, calcium and glutamate-mediated excitotoxicity, increased ROS production causing DNA damage, mitochondrial dysfunction, oxidative stress, development of brain edema, and microvascular dysfunction. To date, tissue plasminogen activator (tPA) therapy and mechanical removal of blood clots are the only clinically available stroke therapies, approved by Food and Drug Administration (FDA). But because of the narrow therapeutic window of around 4.5 h for tPA therapy and complications like systemic bleeding and anaphylaxis, more clinical trials are ongoing in the same field. Therefore, using nanocarriers with diverse physicochemical properties is a promising strategy in treating and diagnosing stroke as they can efficiently bypass the tight blood-brain barrier (BBB) through mechanisms like receptor-mediated transcytosis and help achieve controlled and targeted drug delivery. In this review, we will mainly focus on the pathophysiology of stroke, BBB alterations following stroke, strategies to target BBB for stroke therapies, different types of nanocarriers currently being used for therapeutic intervention of stroke, and biomarkers as well as imaging techniques used for the detection and diagnosis of stroke.
