Table 4.

The summary of NP formulations that have been developed in vitro or in vivo for the treatment of PD

Nanocarrier	Drug	Targeting ligand	Size [nm]	Route [intended route]	Model	Remark	Ref.
PLGA	None	None	50–100	Intracerebral injection	PD mouse model	PLGA‐NP efficiently reduced lysosomal membrane permeabilization in 1‐methyl‐4‐pheynol‐1,2,3,6‐tetrahydropridyine (MPTP)‐injected mice	[ 245 ]
Gold NPs functionalized with chitosan	Plasmid DNA (anti‐α‐Syn short hairpin RNA‐encoding)	NGF	10	i.p.	PD mouse model	NPs crossed BBB. NPs significantly recovered the density of the nigra‐striatum compared to untreated PD models	[ 247 ]
PEG‐dendrigraft poly‐l‐lysine (third generation, 123 primary amino groups)	Plasmid DNA (encoding human glial cell‐line derived neurotrophic factor)[hGDNF]	Angiopep‐2 [TFFYGGSRGKR NNFKTEEYC], targets LRP	119 ± 12	i.v.	PD rat models	Animals acquired improved locomotor activity after five injections	[ 252 ]
PEG‐poly(amidoamine) (PAMAM) dendrimer (fifth generation)	Plasmid DNA [hGDNF]	Lactoferrin a)	196 ± 10.1	i.v.	PD rat models (6‐hydroxydopamine‐lesioned)	NPs improved locomotor activity of the animals following five alternate day injections (three before the formation of brain lesions and two after brain lesions) NPs significantly enhanced exogenous gene expression in the brain by ≈ 5.2‐folds compared to NPs without lactoferrin	[ 249 ]
PEG‐poly(amidoamine) (PAMAM) dendrimer (fifth generation)	Plasmid DNA [hGDNF]	Lactoferrin	196 ± 10.1	i.v.	PD rat models (rotenone‐induced model)	NPs enhanced expression of hGDNF 4.8 folds in the brain, but less than NPs decorated with lactoferrin	[ 253 ]
PEG‐PLA	Urocortin b)	Lactoferrin	120	i.v.	PD rat models	NPs attenuated the striatum lesions and improved behavioral outcomes.	[ 254 ]
Positively charged PLGA	MicroRNA‐124 (surface adsorbed on NPs)	None	210	Intracerebrally	PD mouse model	NPs improved motor activity of the animals	[ 251 ]
Polyethylenimine –dextran sulfate‐Retinoic acid c)	Retinoic acid	None	220	Intrastriatal injection	MPTP) induced mouse model of PD	RA‐NPs increased mRNA levels of Pitx3 (a transcription factor) and resulted in a significant decrease in dopaminergic neuron loss	[ 255 ]
PEG‐PLGA‐odorranalectin d)	UCN	None	114.8 ± 5.6	Intranasal	PD rat model	Systemic adsorption of NPS and accumulation in the liver Conjugating NPs with OL increased accumulation of NPs in the brain compared to unconjugated NPs UCN loaded NPs reduced the number of rotations (a behavioral test representing loss of dopaminergic neurons) in rat models of PD compared to untreated control PD model animals	[ 256 ]
Chitosan	Selegilline hydrochloride	Tween 80	303.39 ± 2.01	Intranasal	In vitro	Release of active ingredient over 28 h	[ 257 ]
Gold nanoflowers	l‐DOPA (via LAT‐1) e)	l‐DOPA	90	i.v.	In vitro	The NPs did not induce neuroinflammation.	[ 258 , 259 ]

^a)Mammalian cationic iron‐binding glycoprotein, which belongs to the Tf family

^b)Urocortin (UCN), a corticotropin‐releasing hormone family of peptides (4 kDa, around 40 amino acids) with restoration of nigrostriatal function property

^c)Retinoic acid (RA) plays an essential role in the commitment, maturation and survival of neural cells

^d)Odorranalectin (OL) is a small molecule of the lectin family with minimal immunogenicity and bioadhesive properties

^e)LAT‐1: Large neutral amino acid transporter.