Advanced drug delivery system against ischemic stroke

Ischemic stroke is a vascular central nervous system (CNS) disease that leads a disability and death. Thrombolysis and neuroprotection are the primary treatment strategies of ischemic stroke. Recombinant tissue plasminogen activator (tPA) is currently the only therapeutic drug approved by the Food & Drug Administration (FDA) for the treatment of ischemic stroke, while the application of tPA is limited by narrow therapeutic window, rapid drug elimination, and risks of hemorrhagic transformation. Blood brain barrier (BBB) poses serious challenges to drug delivery into the brain, leading to many neuroprotective agents failing clinical trials. The drug delivery systems (DDS), including targeted nanocarriers and stimuli-responsive nanocarriers, could protect drugs from elimination, deliver drugs to desired sites such as thrombus and CNS, and specifically release drugs in preferred areas by responding to internal or external stimuli, thus increasing the therapeutic effects of drugs. This review summarizes some strategies employed in nanocarriers to achieve thrombus targeting or enhance the accumulation of neuroprotective agents in the brain and even ischemic regions and brain cells. Meanwhile, the stimuli responsive nanocarriers in response to different internal and external environments of thrombus or ischemic brain parenchyma are systematically discussed. This work also provides insights into the precise treatment of ischemic stroke.