Table 4.

Curcumin-loaded lipid nanoparticles studied in in vitro and in vivo models of neurodegenerative diseases.

Disease	Nanoformulation Type	Model/Administration Route	Outcomes
AD	Solid lipid nanoparticles	In vitro: Mouse neuroblastoma cells after Aβ 1 exposure	Decreased ROS production, Prevented apoptotic death, Inhibition of Tau formation [89,90].
AD	Solid lipid curcumin particle (SLCP), Longvida®	In vitro: lipopolysaccharide (LPS)-stimulated RAW 264.7 cultured murine macrophages.	Improved solubility over unformulated curcumin, Decreased LPS induced pro-inflammatory mediators NO, PGE2, and IL-6 by inhibiting the activation of NF-kB [92].
AD	Solid lipid particleswith CU (SLCP)	In vivo: one-year-old 5xFAD-and age-matched wild-type mice, intraperitoneal injections of CU/SLCP	Decrease in Aβ plaque loads in dentate gyrus of hippocampus, More anti-amyloid, anti-inflammatory, and neuroprotective [91].
AD	Solid lipid nanoparticles	In vivo: Rat, oral	Effective delivery across the BBB 2 [88].
HD	Solid lipid nanoparticles (CU-SLNs)	In vivo: (3-NP)-induced HD in rats	Restored glutathione levels and superoxide dismutase activity, Activation of nuclear factor-erythroid 2 antioxidant pathway, Reduction in mitochondrial swelling, lipid peroxidation, protein carbonyls and reactive oxygen species [89].
CNS disorders	Solid lipid nanoparticles (CU-SLNs) and nanostructured lipid carriers (CU-NLCs)	In vivo: male Sprague−Dawley rats 6−8 weeks old, oral	Enhanced curcumin brain uptake, Cur-NLCs enhance the absorption of brain curcumin more than 4-folds in comparison with Cur-SLNs [95].
AD	Lipoprotein (LDL)-mimic nanostructured lipid carrier (NLC) modified with lactoferrin (Lf) and loaded with CU	In vivo: Rat, oral	Cellular uptake mediated by the Lf receptor, Permeability through the BBB and preferentially accumulation in the brain, Efficacy in controlling the damage associated with AD [96].
AD	Liposomes functionalized with TAT-peptide	In vitro	Permeability across the BBB enhanced [98].
AD	Liposomes containing cardiolipin	In vitro: SK-N-MC cells	Inhibition of the phosphorylation of p38, JNK, and tau protein, Protection against serious degeneration of Aβ insulted neurons [101].
AD	WGA 3-conjugated and cardiolipin-incorporated liposomes carrying NGF 4 and CU	In vitro: Human astrocytes and to protect SK-N-MC cells Apoptosis induced by β-amyloid1–42 (Aβ 1–42) fibrils	Increased entrapment efficiency of NGF and CU, of NGF release and cell viability, Decreased release of CU, Permeability of NGF and CU across the blood–brain barrier [102].
AD	Liposomes	In vivo: Mice, stereotaxic injection in the right hippocampus and neocortex	Decrease in Aβ secretion and toxicity [97].
AD	Liposomes decorated with anti-transferrin receptor mAb	In vivo injection, hippocampus and neocortex	Decrease in Aβ 1–42 aggregation, Internalization in the BBB model [99].
AD	Liposomes functionalized with a curcumin-alkyne derivative TREG	Human biological fluids from sporadic AD patients and down syndrome subjects	Sequestration of Aβ 1–42 [100,101].
Neuronal loss	Liquid-crystalline lipid nanoparticles carrying curcumin and DHA	In vitro: SH-SY5Y cells	Neuronal viability and neurite outgrowth by activation of the TrkB receptor signaling, and promotion of phosphorylated CREB protein expression [118].
AD	Lipopeptide: a short microtubule- stabilizing peptide conjugated to a hydrophobic palmitic acid chain	In vitro: Neuro-2a cells, PC-12 differentiated cells	Neurite outgrowth in absence of external growth factors, Neural cells morphology and health amelioration [120,121].

¹ Aβ-amyloid; ² Blood-brain barrier; ³ Wheat germ agglutinins; ⁴ Nerve growth factor.