Table 1.

Summary of various recently developed surface-modified nanocarriers for drug delivery to the brain.

Type of Nanocarrier	Surface	Core (Drug/Gene)	Clinical Application	Size (nm)	Zeta Potential (mV)	Key Properties	Refs.
PLA Nanoparticles	Lectin and PEG	Wheat germ agglutinin	Brain drug delivery	85-90	-	Negligible nasal ciliatoxicity, higher uptake in rats’ brains.	[19]
Angiopep conjugated nanoparticles	Angiopep and PEG	Dendrigraft poly-L-lysine (DGL)	Neuroprotective Effect	119±12	8.2±0.7	Higher cellular uptake and gene expression in brain cells improved locomotory activity in rats.	[20]
PLGA Nanoparticles	Chitosan	Chlorpromazine hydrochloride	Schizophrenia	463.9 12	+ 21.0 2.0	Increased mucoadhesive particles in sheep nasal mucosa.	[32]
Human serum albumin nanoparticles	Chitosan	sulforhodamine B sodium salt	Neuroprotective Effect	261⌖8	+45⌖1	Higher cellular uptake and increased permeation in rabbit nasal mucosa.	[34]
Solid Lipid Nanoparticle	Chitosan	Ferulic acid	Alzheimer’s disease	185	+12.4	Higher permeation and neuroprotective effect in rats.	[36]
Nanostructured lipid Carriers	Delonix regia gum	Ondansetron hydrochloride	Brain drug delivery	92.28-135	-11.5 to -36.2	higher drug targeting efficiency and direct transport percentage observed in rats.	[38]
Nanoparticles	Alginate	Venlafaxine	Depression	173.7 ± 2.5	37.40 ± 1.74	Increased permeation across nasal mucosa, sustained drug release, improved locomotory in albino Wistar rats.	[39]
Nanoemulsion	N,N,N'trimethyl chitosan	Ropinirole hydrochloride	Parkinson's Disease	32.39 to 99.00	-28.5 to -38.5	Higher uptake in the brain of swiss albino mice improved CNS bioavailability	[40]
Nanoparticles	Butylglyceryl polysaccharides	Doxorubicin, rhodamine B, angiotensin II	Brain disorders	-	-	Increased biological membrane permeability and cellular uptake	[41]
PLGA Nanoparticles	Solanum tuberosum lectin and PEG	Haloperidol	Schizophrenia	<150nm	-11 to -16	Increases the efficacy of particle transport across the nasal epithelium and increases the concentration in the brain of rats.	[44]
Liposomes	Glutathione and PEG	-	Brain drug delivery	108	-	Stability and prolonged circulation time in rats	[46]
Poly propyleneimine dendrimers	Angiopep-2 and PEG	Paclitaxel	Brain cancer	47±0.20 nm	-	Targeted delivery to the brain	[48]
Poly-(amido amine) dendrimers	PEG	Rhodamine B isothiocyanate	Brain ischemia	24.2 nm ± 16.2 nm	11.4 ± 1.69	Increased bioavailability in the neuron, diffusion of the dendrimers through the brain tissue of mice.	[49]
PLGA Nanoparticles	PEG	Brucine	Cancer	94 ± 3.05 to 253 ± 8.7 nm	1.09 ± 0.15 to 3.71 ± 0.44 mV	Decrease in tumor growth in tumor-bearing mice.	[50]
Solid silica Nanoparticles	PEG	MnO2 (H-MnO2)	Stroke	-	-	Protective effect on ischemic stroke mice model	[51]
Nanovesicularspanlastics	Span 60 and polyvinyl alcohol	Risperidone	CNS Disorders	300 nm	-46.7 ± 2.19	Showed elasticity to permeate through mucosal membrane, significantly higher concentration in swiss albino mice.	[55]
Chitosan Nanoparticles	Polysorbate 80	Ropinirole hydrochloride	CNS Disorders	201-233	-19.6	Sustained release, stability of particles and higher concentration of drug in the brain of Wistar rats.	[57]
Chitosan nanoparticles	Tween 80, polyethylene glycol 4000, and miltefosine	Berberine	Neuroprotective Effect	> 190	36.3 ± 1.44	Showed neuroprotective and hepatoprotective effects in rats.	[58]
Albumin nanoparticles	Polysorbate 80	Levetiracetam	Epilepsy	153.7 ± 44.8 nm	- 10.8	Increased drug concentration in male Wistar rats.	[59]
PLGA nanoparticles	Polysorbate 80	Thymoquinone	Alzheimer’s disease	226.2 nm	−45.6 mV	Improvement in behavior and cognitive effect in mice model.	[60]
PLGA nanoparticles	Protamine	Tacrine	Alzheimer’s disease	196.43 ± 0.55	22.53 ± 0.32	Sustained release manner and good brain targeting efficiency and brain absolute bioavailability in rats’ model.	[63]
PEG-lipid nanoparticles	Fas ligand antibody	3-n-Butylphthalide (NBP)	Brain ischaemia	60.97 ±7.95nm	-	Effectively delivered to the ipsilateral region of the ischaemic brain, significantly reduced dosages observed in rats.	[64]
PLGA nanoparticles	Anti-transferrin receptor monoclonal antibody (OX26) and anti-Aβ (DE2B4)	Peptide iAβ5	Alzheimeŕs disease	163 ± 3, 166 ± 2	−10.1 ± 0.4, −13 ± 1	Substantial increase in uptake of immune nanoparticles with a controlled delivery of the peptide iA5	[65]
PLGA nanoparticles	Monoclonal anti-transferrin receptor antibody (8D3 mAb).	Thiazolidinedione	Brain drug delivery	65± 1.4	-22.10	Selective interaction with BBB	[66]
Liposomes	Arg-Gly-Asp peptide	Small interfering RNA (siRNA)	Tumor	-	-	Increased distribution of siRNA in tumors and improved therapeutic efficiency in mice.	[76]
Liposomes	Transferrin	Dopamine HCL	Parkinson’s disease	180 nm	+7.5	Higher permeability and increased concentration of dopamine	[89]
Solid Lipid Nanoparticles	Lactoferrin	Docetaxel	Brain Cancer	121.0 ± 5.65	-21.5 +1.2	Increased the targeting potential for brain tumors of swiss albino mice.	[95]
Lipophilic Nanoparticles	Apolipoprotein E3	Model Drug	Brain Drug delivery	103.3 ± 5.5 to 115.7 ± 1.6	−53.0 ± 2.0 to −49.1 ± 8.5	Higher penetration of drug across BBB, apolipoprotein mediated transcytosis. Enhanced pharmacokinetics in Wistar rats.	[101]
Nanoparticles	Folic Acid	Temozolomide	Glioblastoma	58.61	-29.85 ± 0.47	Enhanced anti-cancer activity and improved drug targeting in rat brain	[103]
Nanocubic vesicles	Poloxamer 188 or 407	Olanzapine	Antipsychotic disorders	363–645 nm	-	Increased drug targeting efficiency and bioavailability in rats.	[105]
Human serum albumin-based Nanoparticles	Apolipoprotein E	-	Neuroprotective Effect	197.8±4.8	−42.5±6.3	The active endocytotic uptake mechanism	[106]
Liposomes	Cell-penetrating Peptides	Doxorubicin	Glioblastoma	95	-	Increased cellular uptake and reduced cell viability	[107]
Nanoparticles	Lactoferrin	Dopamine	Parkinson’s Disease	175.3 ± 9.6	-15.7 ± 0.86	Increased dopamine delivery to the brain via the intranasal route.	[108]