Nanomedicines, an emerging therapeutic regimen for treatment of ischemic cerebral stroke: A review

Owing to its intricate pathophysiology, cerebral stroke is a serious medical condition caused by interruption or obstruction of blood supply (blockage of vasculature) to the brain tissues which results in diminished supply of essential nutrients and oxygen (hypoxia) and ultimate necrosis of neuronal tissues. A prompt risks assessment and immediate rational therapeutic plan with proficient neuroprotection play critically important role in the effective management of this neuronal emergency. Various conventional medications are being used for treatment of acute ischemic cerebral stroke but fibrinolytic agents, alone or in combination with other agents are considered the mainstay. These clot-busting agents effectively restore blood supply (reperfusion) to ischemic regions of the brain; however, their clinical significance is hampered due to various factors such as short plasma half-life, limited distribution to brain tissues due to the presence of highly efficient physiological barrier, blood brain barrier (BBB), and lacking of target-specific delivery to the ischemic brain regions. To alleviate these issues, various types of nanomedicines such as polymeric nanoparticles (NPs), liposomes, nanoemulsion, micelles and dendrimers have been designed and evaluated. The implication of these newer therapies (nanomedicines) have revolutionized the therapeutic outcomes by improving the plasma half-life, permeation across BBB, efficient distribution to ischemic cerebral tissues and neuroprotection. Furthermore, the adaptation of some diverse techniques including PEGylation, tethering of targeting ligands on the surfaces of nanomedicines, and pH responsive features have also been pondered. The implication of these emerging adaptations have shown remarkable potential in maximizing the targeting efficiency of drugs to ischemic brain tissues, simultaneous delivery of drugs and imaging agents (for early prognosis as well as monitoring of therapy), and therapeutic outcomes such as long-term neuroprotection.