Table 2. Various nano-carriers used for nose-to-brain delivery in Parkinson’s disease.

Nano-Carrier	Method of Preparation	Name of Drug	Animal Model	Outcome	References
Chitosan Nanoparticle	Ionic gelation	Pramipexole Hydrochloride	Rat	N2B delivery of Pramipexole dihydrochloride loaded chitosan treated group showed significantly highest dopamine concentration (97.38±3.91 ng/g tissue) compared to other treatment groups.	[41]
PLGA Nanoparticle	Nanoprecipitation	Rotigotine	Mice	IN the administration of Rotigotine loaded PLGA nanoparticles showed a higher concentration of Rotigotine in the striatum than in plasma.	[45]
Chitosan Nanoparticle	Ionic gelation	Selegiline	Rat	After IN administration of Selegiline nanoparticles, the concentration of Selegiline was found to be 20 fold higher in the brain compared to oral administration.	[159]
PLGA Nanoparticle	Double emulsification	Rasagiline	Rat	IN PLGA nano formulation of Rasagiline had given a promising PK profile and provided effective treatment for PD as compared to IN solution form of Rasagiline.	[46]
Mucoadhesive Nanoemulsion	Aqueous titration	Rotigotine	Goat nasal mucosa	The Rotigotine mucoadhesive nanoemulsion had a better permeability through nasal mucosa (85.23±0.39%) compared to Rotigotine nano emulsion (65.25±0.13) at 4 hours.	[53]
Nanoemulsion	Aqueous titration	Vitamin E loaded Naringenin	Rat	N2B delivery of Vitamin E loaded Naringenin nanoemulsion improved muscle coordination, grip strength and swimming activity of 6-OHDA induced PD model.	[50]
Nanoemulsion (o/w)	Spontaneous emulsification method, followed by high-pressure homogenization	Resveratrol-loaded vitaminE	Rat	The improved antioxidant activity, increased SOD,GSH and decreased MDA level. Improved brain/blood ratio of the drug. Histopathological studies showed decreased degenerative changes.	[160]
Lipid nanoparticle	Melt-emulsification	GDNF	Mice	N2B delivery GDNF Lipid nanoparticles significantly improved locomotor activity and motor recovery in MPTP induced PD model.	[161]
Mucoadhesive Nanoemulsion	Response surface methodology	Ibuprofen	Mice	MPTP induced Parkinsonian condition significantly reduced striatal dopamine level to 29.92% which was enhanced to 58.21% after IN delivery of Ibuprofen loaded mucoadhesive nanoemulsion	[52]
Nano-Emulsion	High energy emulsification	Selegiline	Rat	IN administered Selegiline nanoemulsion showed high dopamine level (16.61±3.06ng/ml) as compared to rats treated with Haloperidol (8.59±1.00ng/ml)	[51]
Chitosan Nanoparticle	Ionic gelation	Ropinirole Hydrochloride	Rat	IN administered Ropinirole hydrochloride loaded Chitosan nanoparticles showed higher concentration in the brain at all the time points compared to IN. Ropinirole Hydrochloride administration.	[162]
Micellar thermo-responsive hydrogel	Solvent evaporation	Rotigotine	Rat	Compared to intravenous route, accumulation in the olfactory bulb, cerebrum, cerebellum and striatum was 276.6%, 170.5%, 166.5% and 184.4%, respectively.	[163]
TAT functionalized micelles	Thin film dispersion method	-	Rat	TAT functionalization diminished the retention of micelles in the nasal cavity and brain uptake via trigeminal nerve was observed.	[164]
Liposomes	Thin film dispersion	Glial cell line-derived neurotrophic factor	Rat	A substantially greater neurotrophic effect was observed with increase in tyrosine hydroxylase positive neurons with greater neuroprotective ability determined by TH immunostaining was observed.	[165]
Solid-lipid Nanoparticle	Emulsification solvent diffusion	Ropinirole Hydrochloride	Mice	Nasal formulation of solid lipid nanoparticles of Ropinirole hydrochloride significantly reduced tremors against the marketed oral formulation.	[57]