The Application of Nanoparticles for Neuroprotection in Acute Ischemic Stroke

Abstract

Stroke still represents one of the most common causes of death and disability worldwide. Acute ischemic stroke (AIS), caused by brain arterial occlusion resulting from a thrombus or embolus, is the most common form of stroke. However, current therapies in AIS are inadequate, and the only US FDA approved treatment is the thrombolytic drug Alteplase. Therefore, establishing effective therapeutic strategies for AIS is urgently needed. Using nanoparticle-based technologies to deliver neuroprotective agents to the ischemic area has attracted increasing attention of late. In this review, the important molecular pathological mechanisms in cerebral ischemia are briefly summarized, the potential of nanoparticulate drug-delivery systems for AIS intervention and recovery are introduced and problems in the medical application of nanoparticles will also be discussed.

Nanomedicine for Ischemic Stroke

“…Many drugs, such as adenosine [ 46 ], have been developed and approved by the FDA to treat myocardial ischemia. However, they failed to be used in treating cerebral I/R injury [ 47 ] because they have the short plasma half-life time and lack of permeability to BBB. To address this issue, nanoparticle drug delivery systems have been developed to deliver drugs to cross BBB.…”

Recent Advances in the Therapeutic and Diagnostic Use of Liposomes and Carbon Nanomaterials in Ischemic Stroke

“…The reduced permeability of BBB to most drugs, including imaging contrast agents, macromolecular compounds, nucleic acids and proteins ( Hawkins and Davis, 2005 ; Gabathuler, 2010 ; Essig et al, 2012 ; Tam et al, 2016 ) represents a major obstacle to the development of safe and effective diagnostic and treatment strategies for ischemic stroke ( Mouhieddine et al, 2015 ). Even knowing that during ischemia/reperfusion there is a rupture in the BBB structure, this opening is transitory and the amount of drug that can actually reach the tissue is often not enough to produce the desired effect, especially in the case of macromolecular drugs ( Chen and Gao, 2017 ; Merali et al, 2017 ). In this context, there has been much interest in the design of nanoparticles capable of carrying therapeutic and diagnostic agents across the injured and normal BBB and targeting the ischemic tissue and the penumbra region of the damaged tissue ( Kafa et al, 2015 ; Mendonça et al, 2015 ; Fukuta et al, 2016 ; Zhao Y. et al, 2016 ).…”

“…Regarding therapeutic options for acute ischemic stroke, only two are available: thrombolysis and mechanical thrombectomy, both strategies focusing on reperfusion therapy. Thrombolysis is the leading treatment for acute stroke, performed by a pharmacological intervention using recombinant tissue plasminogen activator or t-PA, the only available treatment approved by the US FDA ( Chen and Gao, 2017 ). However, a small number of stroke victims can actually use t-PA treatment since it has a narrow time window of treatment efficacy on the eligible patients (4–5 h of symptom onset), and an increased risk of intracerebral hemorrhage ( Khandelwal et al, 2016 ).…”

“…It is crucial that liposomes can cross the BBB and it is also desirable that they remain in the bloodstream for a long period of time, so as to deliver a sufficient quantity of drug to the brain tissue ( Moghimi et al, 2001 ). The circulation time of liposomes can be enhanced through reduction of particle size or modification of their surface by polyethylene glycol (PEG) ( Fukuta et al, 2014 ; Bozzuto and Molinari, 2015 ; Wang et al, 2015 ; Campos-Martorell et al, 2016 ; Chen and Gao, 2017 ). It has been reported that PEGylated liposomes can accumulate into ischemic brain regions after a stroke event ( Fukuta et al, 2016 ), presumably because of the disruption of the BBB and the enhanced vesicle permeation and retention at the ischemic site.…”

Trends in Tissue Regeneration: Bio-Nanomaterials

“…Diversity in organic materials derived mainly from polymers, such as polysaccharides, collagen, and chitosan have been recently used with different morphologies into the biomedical application and stem cell differentiation [19]. In particular, the use of polymer NPs as carriers or drug delivery systems is promising materials used as neuroprotectors to avoid acute ischemic stroke, which is actually considered one of the most common causes of death worldwide [40]. Nanostructured drug delivery systems offer many advantages, such as the avoidance of drug degradation, the possibility to improve the pharmacokinetic profile and the specificity at nano scale.…”