Table 3.

Summary of recent research work on the delivery of NPs for the treatment of ischemic stroke

Nanocarrier	Drug	targeting Ligand	Size [nm]	Route	Model	Remarks	Ref.
PEG‐liposomes	ZL006, a neuroprotective agent	T7 (HAIYPRH)[brain targeting] + SHp (CLEVSRKNC) [stroke homing]	96.24 ± 1.13	i.v.	MCAO‐rat	Liposomes remained in the ischemic region after 24 h significant decrease of cell death much reduced infarct volume (from 60% to 30%	[ 234 , 235 ]
PLGA (poly(ε‐carbobenzoxyl‐l‐lysine)	Lexiscan (modulates the BBB and hence allows more NCs to cross the BBB) + NEP1‐40 ‐a 40‐amino acid peptide, an antagonist of Nogo‐66	Chlorotoxin (targeting MMP‐2)	151.8	i.v.	MCAO‐mouse	NPs reduced the infarct area (from 40% to 20%)	[ 236 ]
Liposomes	Fasudil (Rho kinase inhibitor with neuroprotective effects in ischemic stroke)	None	126.8 ± 3.1 nm	i.v.	MCAO‐rat	tPA administered i.v. prior to administration of NPs to activate MM‐2 and MMP‐9 leading to increased BBB permeability Fasudil liposomes significantly suppressed brain cell damage	[ 237 ]
PEG‐liposomes	Asialo‐erythropoietin	None	ND	i.v.	t‐MCAO‐rat	Liposomes prevented brain damages because of reperfusion after ischemic stroke AEPO‐liposomes ameliorated neuronal apoptosis AEPO‐liposomes recovered from the paralysis of the right paw	[ 238 , 239 ]
Liposomes	Fasudil	None	100	i.v.	t‐MCAO‐rat	Reduced infarct volume (from 0.4 to 0.2 cm3) Improved motor function deficits (from motor score 9 to motor score 12 on a 21‐point neurological assessment scale)	[ 240 ]
squalenoyl adenosine	Adenosine	None	120	i.v.	ischemic‐reperfusion rat model	Reduced infarct volume from 54 ± 3 mm3 (vehicle treated) to 24 ± 4 mm3	[ 241 ]
PLGA‐PEG	Thyroid hormone	Glutathione	326.6	i.v.	MCAO‐mouse	As well as NPs coated with glutathione, uncoated NPs also significantly reduced infarct volume	[ 242 ]
Chitosan	Z‐DEVD‐FMK a)	TfR antibody	637 ± 2	i.v.	MCAO‐mouse with reperfusion	NPs reduced infarct volume from 43 ± 4 mm3 (control) to 3 ± 2 mm3. NPs released sufficient amounts of the active ingredient to prevent activation of caspase 3 following reperfusion.	[ 243 ]

^a) N‐benzyloxycarbonyl‐Asp(OMe)‐Glu(OMe)‐Val‐Asp(OMe)‐fluoromethyl ketone.

AEPO: Asialo‐erythropoietin