Application and Utility of Liposomal Neuroprotective Agents and Biomimetic Nanoparticles for the Treatment of Ischemic Stroke

Abstract

Ischemic stroke is still one of the leading causes of high mortality and severe disability worldwide. Therapeutic options for ischemic stroke and subsequent cerebral ischemia/reperfusion injury remain limited due to challenges associated with drug permeability through the blood-brain barrier (BBB). Neuroprotectant delivery with nanoparticles, including liposomes, offers a promising solution to address this problem, as BBB disruption following ischemic stroke allows nanoparticles to pass through the intercellular gaps between endothelial cells. To ameliorate ischemic brain damage, a number of nanotherapeutics encapsulating neuroprotective agents, as well as surface-modified nanoparticles with specific ligands targeting the injured brain regions, have been developed. Combination therapy with nanoparticles encapsulating neuroprotectants and tissue plasminogen activator (t-PA), a globally approved thrombolytic agent, has been demonstrated to extend the narrow therapeutic time window of t-PA. In addition, the design of biomimetic drug delivery systems (DDS) employing circulating cells (e.g., leukocytes, platelets) with unique properties has recently been investigated to overcome the injured BBB, utilizing these cells’ inherent capability to penetrate the ischemic brain. Herein, we review recent findings on the application and utility of nanoparticle DDS, particularly liposomes, and various approaches to developing biomimetic DDS functionalized with cellular membranes/membrane proteins for the treatment of ischemic stroke.

Recent Advances in Cell‐Based Nanotherapy for Cardiovascular Diseases

“…As stroke is a sudden reduction of cerebral blood flow by vessel occlusion, thrombolysis therapy remains a frequently-used approach for stroke. [76] Recombinant-based plasminogen activators (PA) (e.g., alteplase (rtPA)) have been approved by US FDA as "clot busters" drugs for thrombotic diseases. [53,77] Unfortunately, their practical application was hindered by rigorous clinical indications and complications including limited thrombolytic efficacy and less than 4.5 h of time from symptom to treatment.…”

DTI-ALPS: An MR biomarker for motor dysfunction in patients with subacute ischemic stroke

“…Ischemic stroke (IS) remains one of the leading causes of disability and death worldwide (Campbell et al, 2019;Campbell and Khatri, 2020;Fukuta et al, 2022). Approximately 69.6% of stroke incidents in China are IS, similar to the global average (Wang W. et al, 2017;Feigin et al, 2018).…”

Biomimetic nanoparticles in ischemic stroke therapy

“…In order to increase the drug concentration in local tissue effectively, biomimetic membrane-based DDS coated with various BBB transport vectors (such as cell-penetrating peptides, antibodies, ligand-mimicking peptides and magnetic molecules) are widely investigated. Indisputably, nanomedicine, especially the biomimetic nanomedicine, has played an increasingly important role in cerebral disorders therapy, enabling new strategies for the medical intervention of ischemic stroke [ 19 ].…”