Curcumin-loaded nanoparticles: a novel therapeutic strategy in treatment of central nervous system disorders

Figures & data

Figure 1 Nano-based drug delivery system for targeted delivery and enhancement of water solubility and bioavailability of curcumin.

Abbreviation: CNS, Central nervous system.

Table 1 In vitro application of nano-curcumin

Nano-Cur	Cellular model	Disease	Key Finding	Ref.
Curcumin-loaded PLAG NPs	Neuroblastoma cell line (SK-N-SH cells)	AD	Inhibition of Nrf2, NF-kB and Akt phosphorylation Tau/↓ Expression of APOJ/↑ Expression of GLRX and TRX	^Citation45
g7-NPs-Cur	Primary hippocampal cell cultures/Aß (1–42)	AD	↓ Oxidative stress/↓ Inflammation/↓NF-kB/↑IkB//↑ Aß disaggregation	^Citation42
PLGA-PEG-B6/Cur	HT22 cells	AD	Narrowing the diameter of Cur/↑Cellular uptake	^Citation48
Alginate-curcumin nanocomposite (ACNC)	α-synuclein-induced cytotoxicity in SH-SY5Y neuroblastoma cells	PD	Apoptosis↓/Postpone the loss of climbing ability/Preventing caspase 3 activation/↓ Oxidative damage/↓ Cytotoxicity of accumulated α-synuclein	^Citation54
LF-NP-Cur	Rotenone-induced toxicity in SK-N-SH cells	PD	↓ ROS levels/Suppression of α-synuclein expression/↑ Expression of TH enzyme	^Citation53
GMO-NP-Piperine/Curcumin	Dopaminergic neurons against rotenone-induced degeneration model	PD	↓ Aggregation of α-synuclein/↓ Motor dysfunction/↓ Oxidative stress/↓ Apoptosis/Enhancing the autophagy/↑ Density of TH positive neurons	^Citation56
BSA-based nano-curcumin	6-hydroxydopamine (6-OHDA)-induced death and Akt signaling disruption in SH-SY5Y cells	PD	Corrected p-Akt/t-Akt signaling/prevent cell death	^Citation60
Curcumin and fish oil-loaded spongosome and cubosome NPs	H2O2-induced oxidative stress in differentiated human SH-SY5Y cells	PD	↓ H2O2-induced cell death/ ↓ ROS accumulation	^Citation58
Insulin-d-alpha-tocopherol succinate micelles (INVITE)–loaded curcumin micelles	Mesenchymal stromal cells (MSCs)	ALS	Maximum loading in MSCs/no cytotoxicity	^Citation79

Abbreviations: PLGA, Poly (lactic-co-glycolic acid); NPs, Nanoparticles; AD, Alzheimer’s disease; Cur, Curcumin; PEG, Polyethylene; PD, Parkinson’s disease; LF, Lactoferrin; ROS, Reactive oxygen species; TH, Tyrosine hydroxylase; GMO-NP, Glyceryl monooleate-nanoparticle; BSA, Bovine serum albumin; ALS, Amyotrophic lateral sclerosis.

Table 2 In vivo application of nano-curcumin in CNS related disorders

Nano-Cur	Animal model	Disease	Key findings	Ref.
PLGA (2 mg/kg)	APP/PS1dE9 mice	AD	↓ Aß42/↓ Aß 40/↑ SOD ↓ TNF-α/↓ IL6/↓ROS/↑ Synapse number/Inhibit APP cleavage/Suppress microgliosis and astrogliosis	^Citation83
Cur-PLGA-NPs (5,10, and 20 mg/kg)	Aβ-induced rat model of AD	AD	↑ Pax6 and reelin expression/↑ NSCs proliferation, Self-renewal, Neuronal differentiation/↓ Expression of Axin12, APC, GSK-3ß/↑ Cyclin-D1 and TCF/LEF Promoter activity expression of Wnt3, LRPP-5, LEF/↓ Expression of Wif-1,Dkk-1/↑ p-GSK-3β cells/↓ p-β-catenin cells/↑GSK-3β phosphorylation/↓ phosphorylation of β-catenin	^Citation37
Selenium/Curcumin-PLGA nanosphere	Transgenic mice 5XFAD	AD	↓ Aß aggregation and toxicity	^Citation38
Low density lipoprotein mimic nanostructured lipid carrier modified with lactoferrin-loaded curcumin (6 mg/kg)	Administrating Aβ1-42 and D-gal in rats	AD	↓ MDA level/↓ Damage associated with oxidative stress/↓ Lipid peroxidation	^Citation39
CRT-conjugated PLGA 2 mg/kg (i.p.)	AD transgenic mice	AD	↓ Activated glial cell/↑ Number of synapses/↓ IL-6, TNF-α/Restore antioxidant activity (↓ ROS)/↑ SOD/↑ Spatial memory/Enhanced behavioral deficit/Suppress astrogliosis and microgliosis	^Citation44
Curcumin-loaded PEG-PLA NPs (23 mg/kg)	Tg2576 mice	AD	Enhanced cue memory	^Citation35
PLGA-PEG-B6/Cur	APP/PS1 mice	AD	Enhance the spatial learning and memory capability/Inhibit the generation of BACE1, APP, and PS1/↓ tau phosphorylation and Aß aggregation	^Citation48
Alginate-curcumin nanocompposite	Transgenic Drosophila model	PD	↑ Bioavailability/↓ Oxidative stress/↓ Apoptosis	^Citation54
Curcumin-loaded polysorbate 80-coated cerasome NPs with UTMD (15 mg curcumin/kg)	PD mouse model induced by 1-methyl-4-phenyl-1, 2, 3, 6, tetrahydropyridine (MPTP)	PD	↓ PD symptoms/↑ Circulation time in blood	^Citation55
Curcumin encapsulated solid lipid NPs (40 mg/kg)	In 3-nitropropionic acid-induced-(3-NP) Huntington’s disease model in rats	HD	Enhance mitochondrial activity (↑ activity of NADH dehydrogenase/↑ SDH activities/↑ cytochrome oxidase)/↓ Mitochondrial swelling/↓ MDA, protein carbonyl and ROS/↑ GSH and SOD enzymes/↑ Expression of Nrf2/↑ Locomotor activity	^Citation62
Polymerized nano-curcumin (12.5 mg/kg)	Experimental autoimmune encephalomyelitis (EAE) model of MS	MS	↑ IL-4 ‚IL-10‚ TGF-ß/↑ FOXP3/↑ Expression of HO-1 gene/Induction of Nrf2 signaling pathway/↓ iNOS mRNA level/↑ MBP expression level/↑ Expression levels of nestin, Olig2 and PDGFR-α/↑ BDNF and NGF levels	^Citation66
Curcumin-loaded NPs (12.5 mg/kg, i.p.)	Lysolecthin-induced focal demyelination model of rat corpus callosum	MS	↓ Glial activation/↑ Myelin repair/↓ Immune cells infiltration /↓ Extent of demyelination areas	^Citation67
Curcumin NPs (20, 40, 80 mg/kg,) (i.p.)	Pilocarpine-induced status epilepticus (SE) model in rats	Epilepsy	↓ Lipid peroxidation/↑ GSH and NO/↓TNF-α/↓ Caspase 3/↓ iNOS expression/↑ Latency to PTZ-induced clonic seizures	^Citation73
Liposomal formulation of curcumin(25 and 50 mg/kg)	Status epilepticus model in mice	Epilepsy	↑ Latency to PTZ-induced myoclonic jerk and generalized seizures/↓ Duration of clonic seizures	^Citation74
Curcumin-loaded NPs (12.5 mg/kg, i.p.)	Pentylenetetrazol (PTZ)-induced kindling model	Epilepsy	↓ Neuronal cell death/↑ Levels of EPO and klotho/↓ mRNA level of TNF-α	^Citation75
Chitosan-alginate-sodium tripolyphosphate nanoparticles (12.5 or 25 mg/kg, i.p.)	PTZ-induced kindling model	Epilepsy	↑ Spatial learning and memory/↓ Cell death and glial activation	^Citation76

Abbreviations: PLGA, Poly (lactic-co-glycolic acid); NPs, Nanoparticles; APP, Amyloid precursor protein; AD, Alzheimer’s disease; SOD, Superoxide dismutase; ROS, Reactive oxygen species; NSCs, Neural stem cells; PEG-PLA, Polyethylene glycol- polylactic acid; PD, Parkinson’s disease; HD, Huntington’s disease; MS, Multiple sclerosis; SDH, Succinate dehydrogenase; MDA, Malondialdehyde; GSH, Reduced glutathione; iNOS, Inducible nitric oxide synthase; MBP, Myelin basic protein; PDGFR, Platelet-derived growth factor receptor; BDNF, Brain-derived neurotrophic factor; NGF, Nerve growth factor.

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