Table 1.

Summary of native EVs/exosomes for brain drug delivery and therapy in preclinical studies

Exosomes/MVs source	Cargo	Administration route	Brain disease (animal model)	Reference
Macrophages	catalase	intranasal or intravenously injected	Parkinson’s disease	Haney et al.49
EL-4 T cells	curcumin	intranasal administration	brain inflammation	Zhuang et al.50
bEnd.3 cells	doxorubicin	intravenous injection	glioblastoma	Zhang et al.59
HEK293T	Cre recombinase	intranasal delivery	across the BBB	Sterzenbach et al.60
Human bone marrow-derived mesenchymal stem cells (hBM-MSCs)	glucose-coated gold nanoparticle (GNP)	intranasal administration	stroke model	Betzer et al.61
Human adipose mesenchymal stem cell (hADSC)	miR-124	intracerebroventricular	ischemic stroke	Wang et al.55
MSCs	miRNA-17-92	intravenous	ischemic stroke	Xin et al.62
Gingival MSC	TNF-α-stimulated	intraocular injection	retinal ischemia-reperfusion injury	Yu et al.63
Macrophages	lipopolysaccharide (LPS)-stimulated	intravenous injection	ischemic stroke	Zheng et al.64
Macrophages	curcumin	tail vein injection	ischemia-reperfusion injury	He et al.65
MSC	–	tail vein injection	intracerebral hemorrhage	Han et al.66
Blood	dopamine	intravenous injection	Parkinson’s disease	Qu et al.26
Plasma	edaravone	intravenous injected into rats via tail vein	ischemic stroke	Guo et al.67
MSC	–	intravenous	Parkinson’s disease	Chen et al.68
Bone marrow-derived MSCs (BM-MSCs)	SDF-1alpha	intravenous	PD rat model	Cova et al.69
BM-MSCs	–	intravenously injected by tail vein	stroke	Xin et al.57
BM-MSCs	–	tail vein injection	traumatic brain injury	Zhang et al.70
Human umbilical cord mesenchymal stem cells (hUC-MSCs)	–	injection	Alzheimer’s disease	Ding et al.71
hUC-MSCs hBM-MSCs	–	intranasally administered	autism mouse model	Liang et al.53; Perets et al.72