Table 1.

Neuroprotective agents tested under liposomal form against ischemic stroke.

Neuroprotective agent	Liposome characteristics	Stroke model	Main findings	Reference
Panax notoginsenoside	Core-shell hybrid liposomal vesicles	Bilateral common carotid artery occlusion (BBCAO)	Oral administration with inhibition of brain edema, reduction of infarct volume and increase in superoxide dismutase	Zhang et al., 2012
t-PA/ dexamethasone	PEGylated liposomes	MCAO by thromboembolic ischemia	Intravenous injection with improvement of behavioral outcome	Tiebosch et al., 2012
FK506	PEGylated liposomes	Transient middle cerebral artery occlusion (t-MCAO)	Intravenous injection with accumulation of liposomes in the brain parenchyma, reduction of cerebral cell death and improvement of motor function deficits	Ishii et al., 2013
Citicoline	Targeted PEGylated immunoliposomes labeled with gadolinium	Permanent intracranial occlusion of middle cerebral artery	Intravenous injection with accumulation of 80% vectorized liposomes in the periphery of the ischemic lesion as detected by MRI and reduction of lesion volumes up to 30% in comparison to animals treated with the free drug	Agulla et al., 2014
Basic fibroblast growth factor (bFGF)	Gelatin-cored liposomes	Transient middle cerebral artery occlusion (t-MCAO)	Intranasal administration with increased accumulation of bFGF in the brain, improved neurological score and reduced infarct volume	Zhao Y.Z. et al., 2016
ZL006	Targeted PEGylated liposomes	Transient middle cerebral artery occlusion (t-MCAO)	Liposomes with targeting peptide ligands for both transferrin receptor and stroke tissue accumulated in the brain, ameliorated infarct volume, neurological deficit and histopathological severity in MCAO injury	Zhao Y. et al., 2016
Fasudil	PEGylated liposomes	Transient middle cerebral artery occlusion (t-MCAO)	Intravenous injection with accumulation of liposomes in the ischemic region, amelioration of ischemic/reperfusion injury and motor score	Fukuta et al., 2016
Simvastatin	PEGylated liposomes	Transitory middle cerebral artery occlusion (t-MCAO)	Intravenous injection of neutral and negatively charged liposomes reaching the brain, accumulating in the infarcted area and delivering simvastatin to the brain.	Campos-Martorell et al., 2016
Citicoline	Targeted PEGylated immunoliposomes	Transient middle cerebral artery occlusion (t-MCAO)	Intra-arterial or intravenous injection of citicoline-liposomes (PEGylated or conjugated to targeting vascular cell adhesion molecule 1), with direct detection through the CEST-MRI in the ischemic areas, being a potential theranostic device	Liu et al., 2016
Cyclosporine	PEGylated liposomes	Transient middle cerebral artery occlusion (t-MCAO)	Intravenous injection of CsA-liposomes showing recovery of the infarct size, brain edema and neurological activities, and inhibition of inflammation	Partoazar et al., 2017
t-PA/fasudil	PEGylated liposomes	MCAO by photochemically induced thrombosis (PIT)	Intravenous administration of fasudil-lip before t-PA decreased the risk of t-PA-derived cerebral hemorrhage and extended the therapeutic time window of t-PA	Fukuta et al., 2017
Hemoglobin	PEGylated liposomes	MCAO by transorbital approach	Intravenous administration to nonhuman primates of liposomal hemoglobin was effective in reducing the area of histological damage in the brain cortex	Kawaguchi et al., 2017
Paired immunoglobulin-like receptor B ectodomain (sPirB)	PEGylated liposomes labeled with NIR probe	Transient middle cerebral artery occlusion (t-MCAO)	Intravenous administration of sPirB-containing liposomes with accumulation in the ischemic region and improved ischemic stroke model recovery, showing potential for a new theranostic platform	Wang et al., 2018