Table 1.

Featured novel drug delivery methods in central nervous system disorders in human and animal models.

CNS Disorders	Novel Drug Delivery Methods	Description	References
Epilepsy	Electrophoretic drug delivery	The microfluidic ion pump detects seizure activity and electrophoretically pumps ions across the ion exchange membrane to deliver the localized treatment of inhibitory neurotransmitters, tested in mice.	[19,20]
	Implanted intracerebroventricular delivery system	The system (clinicaltrials.gov identifier NCT02899611) pumps the anti- seizure medication valproic acid into cerebrospinal fluid for long-term treatment in epilepsy patients.	[21]
	Microencapsulation of anti-seizure medications	Polymer cores loaded with the anti-seizure medication lacosamide are covered with drug-free polymer shells, tested in vitro using artificial cerebrospinal fluid.	[22]
	Nanoparticles	Glucose-coated gold nanoparticles are conjugated with the anti-seizure medication lacosamide for intravenous administration in rats.	[23]
		Chitosan–lecithin nanoparticles were loaded with phenytoin for intranasal administration in mice.	[24]
Stroke	Macrophage migration inhibitory factor antagonist ISO-1	Intravenous administration of ISO-1 (4,5-Dihydro-3-(4-hydroxyphenyl)-5-isoxazoleacetic acid methyl ester) following middle cerebral artery occlusion in vivo in rats.	[25]
	Liposomes	T7-conjugated PEGylated liposomes were loaded with neuroprotectant and nNOS/PSD-95 inhibitor ZL006 in vivo in rat and mouse models of stroke.	[26,27]
	Focused ultrasound-enhancedintranasal delivery	Intranasal administration of dextran in vivo in mice was followed by focused ultrasound and systemic administration of microbubbles.	[28]
Brain Cancer	Bioresorbable electronic patch	Patch performs long-term drug release and mild-thermic actuation increases drug permeation in a mouse model of brain tumor.	[29]
	Nanoparticles	Cornell prime dots with αvintegrin-binding/nontargeting peptides and PET labels delivered anti-cancer drug dasatinibin in a mouse model of glioblastoma.	[30]
Traumatic Brain Injury (TBI)	Exosomes	Exosomes derived from mesenchymal stem cells (MSC) containing biologically active molecules that aid in reducing inflammation in TBI; intravenous delivery; can cross the blood-brain barrier, shown in animal models.	[31,32,33]
	Nanoparticles	Poly(lactic-co-glycolic acid) nanoparticles in vivo in mice to deliver siRNA for the treatment of TBI; polysorbate 80-coated nanoparticles for receptor-mediated transport via lipoprotein receptor.	[34,35]
Other CNS Disorders	Supramolecular del (Parkinson’s disease)	Hydrogel loaded with amino acid L-DOPA rapidly releases drug after intranasal delivery in mice.	[36]
	Nanoparticles (Parkinson’s disease)	Protocells were co-loaded with Parkinson’s disease drugs levodopa and curcumin and lipid bilayer was modified for brain targeting via intraperitoneal injection in a mouse model of Parkinson’s.	[37]
	Oral and maxillofacial device (Parkinson’s disease)	Device implanted in the oral or maxillofacial region delivers drug to brain via the respiratory mucosa in an in vivo rabbit model.	[38]
	Magnetic resonance-guided low-intensity focused ultrasound (Alzheimer’s disease)	Magnetic resonance-guided low-intensity focused ultrasound treatment of the hippocampus and entorhinal cortex reversibly opens a large area of blood-brain barrier in humans.	[39]