Table 1.
Nanoformulations of Phytochemicals and Synthetic Drugs in Combating AD and PD
| Disease | Component | Nano Vehicle/Method | Study Type | Results | References |
|---|---|---|---|---|---|
| AD | Phytochemicals Nanoformulations | ||||
| Resveratrol | SLNs; ASDs | In vitro: endothelial cells; In vivo: Aβ/APP/PS1 mouse | ↓formation of Aβ (1–42) aggregates, ↓quick clearance, ↓Aβ plaque density in the cortex, caudoputamen, and hippocampus | [126,184] | |
| NLCs | In vitro: fresh nasal mucosa of sheep; In vivo: male Sprague-Dawley rats | ↑memory function, ↑permeation across nasal mucosa via decreasing the crystallinity of particles through a lipid-oil mixture | [127] | ||
| Curcumin | PLGA; ASDs | In vitro/ in vivo: Tg2576 mice | ↑working and recall memory via activating canonical Wnt/β-catenin pathway, ↑curcumin bioavailability, ↓rate of amyloid and plaque burden | [129,184] | |
| PLGA | In vitro: SK-N-SH cells, a human neuroblastoma cell line | ↑curcumin stability | [131] | ||
| PLGA-PEG-B6 | In vitro: HT22 cells | ↑cellular absorption, ↑blood compatibility | [134] | ||
| In vivo: APP/PS1 mice | ↑spatial learning and memory performance | [134] | |||
| Ex vivo | ↓hippocampus-amyloid production and deposit, ↓tau hyperphosphorylation | [134] | |||
| PLGA | In vitro/in vivo: Wistar rats | ↑NSC proliferation and neuronal differentiation in the hippocampus | [133] | ||
| PLGA | In vivo: Wistar rats | ↑hippocampus neurogenesis, cognition, and memory, ↑canonical Wnt/β-catenin pathway | [133] | ||
| PLGA | In vitro: rat hippocampal cells | ↓Aβ aggregates | [132] | ||
| Nanoliposomes | In vitro: hAPPsw SH-SY5Y cell; In vivo: APP/PS1 mice | ↓Aβ-induced toxicity, ↓Aβ deposits | [135] | ||
| Naringenin | NEs | In vitro: SH-SY5Y cells | ↓APP, ↓BACE, ↓tau phosphorylation | [136] | |
| Quercetin | PLGA; ASDs | In vitro: SH-SY5Y cells; In vivo: Aβ/C. elegan CL2006 | Neurotoxicity of the Zn2+-Aβ42 system, ↑neuron cell survival by suppressing Zn2+-AB42 system, ↓aggregation of proteins | [140,184] | |
| PLGA-NPs | In vivo: APP/PS1 mice | ↑cognitive functions and memory | [140] | ||
| NPQ | In vivo: SAMP8 mice | ↑oral absorption, ↑bioavailability, ↑cognitive and memory | [137] | ||
| NPs | In vivo: male Albino Wistar rats | ↑residence period in the systemic circulation, ↑ bioavailability | [139] | ||
| Cyclodextrin-dodecyl carbonate nanoparticles | In vitro: SH-SY5Y cells | ↓TLR4 and COX-2 signaling pathway, ↑BBB penetration, ↑bioavailability | [138] | ||
| Rosmarinic acid | CRM197-ApoE-PAAM-CH-PLGA | In vitro: SK-N-MC cells | ↓degeneration of Aβ-insulted neurons, ↑BBB transportation, ↓caspase-3, and c-Jun | [141] | |
| Epigallocatechin 3-gallate | Nanolipidic | In vitro: murine neuroblastoma cells; In vivo: male Sprague Dawley rats | ↑neuronal α-secretase, ↑oral bioavailability | [142] | |
| Nano | In vitro: SH-SY-5Y cell | ↓cellular toxicity, ↓Al3+-induced Aβ42 fibrillation, and neurotoxicity | [143] | ||
| Stabilized selenium nanoparticles coated with Tet-1 peptide | In vitro: PC12 cells | ↓Aβ fibrillation, Aβ fibrils into harmless aggregates efficiently | [144] | ||
| Ginsenoside Rg3 | PLGA | In vitro: C6 rat glial cells and THP-1 human monocytic cells line | ↑BBB permeability, ↓formation of Aβ plaques, and eventual neurodegeneration | [150] | |
| Ferulic acid | SLN | In vitro: human neuroblastoma cells (LAN 5) | ↓ROS compared cells | [185] | |
| Berberine | MWCNTs | In vitro: SH-SY5Y cells; In vivo: male Wistar rats | ↑memory function recovery, ↑biochemical levels in brain tissue, and ↓Aβ | [148] | |
| Sesamol | SLN | In vivo: male Wistar rats | ↓neuronal malfunction, ↓ memory impairments by reducing oxidative stress | [146] | |
| Huperzine A | Lf-TMC NPs | In vitro/ex vivo: 16HBE and SH-SY5Y cell lines | ↑mucoadhesion, ↑widely dispersed in the brain over a long period | [149] | |
| Nanoformulations of synthetic drugs | |||||
| Memantine | PEG–PLGA | In vitro/in vivo: APP/PS1 and C57BL/6 mice | ↓Aβ plaques | [156] | |
| Donepezil | Liposome | In vivo: male Wistar rats | ↑brain bioavailability | [154] | |
| Rivastigmine | Liposome | In vivo: male Wistar albino rats | ↑memory recovery, ↓metabolic abnormalities | [152] | |
| SLN | In vitro: Franz diffusion cell | ↑diffusion and not affect nasociliary disruption or cell necrosis | [153] | ||
| Tarenflurbil | NPs/SLN | In vitro: brain cells | ↑brain biodistribution pattern, ↑ the pharmacokinetic behavior | [160] | |
| Estradiol | PLGA | In vivo: male Sprague–Dawley | ↑brain estradiol levels | [158] | |
| Galantamine hydrobromide | SLN | In vitro/ in vivo: male New Zealand rabbits | ↑substantial memory restoration potential, ↑bioavailability | [155] | |
| bFGF | STL-PEG-PLGA | In vivo: male Sprague-Dawley rats | ↓neuronal degeneration, ↓learning impairments, ↑direct transport of bFGF into the rat brain, ↓peripheral adverse reactions | [162] | |
| PD | Phytochemicals Nanoformulations | ||||
| Resveratrol | NPs | In vitro/ in vivo: male albino Wistar rats | ↑resveratrol blood levels for a more extended period, ↑bioavailability, ↑ pharmacological impact | [164] | |
| Lips@Fe3O4 | In vitro/ In vivo: male Sprague-Dawley rats | ↑sustained and delayed drug release, ↑efficiently penetrate the BBB, ↑drug concentration at the targeted area in the presence of an external magnetic field | [165] | ||
| Vitamin E loaded resveratrol NEs | In vitro: brain cells | ↓degenerative alterations, ↑antioxidant effect of resveratrol against hydrogen peroxide | [166] | ||
| PS80-coated poly lactide NPs | Ex vivo: C57BL/6 mice | ↑resveratrol concentration in the brain | [167] | ||
| Curcumin and piperine | GMO-NPs | In vitro: rat PC12 cell line | ↓αS protein oligomerization and fibril formation, ↓rotenone-induced toxicity, ↓GSH depletion induced by rotenone, ↓ration of Bcl-2/Bax, ↑autophagic pathway | [168] | |
| In vivo: male Balb/c mice and male C57BL/6 mice | ↑cross the BBB, ↓rotenone-induced motor coordination impairment, ↓dopaminergic neuronal degeneration | [168] | |||
| Naringenin | Vitamin E loaded NEs | In vitro/in vivo: Wistar rats | ↑muscular coordination, grip strength, ↑swimming activity, ↑naringenin in the brain, ↑ bioavailability, ↑GSH, ↑ SOD, ↓MDA | [169] | |
| Gallic acid | PEI-HAS-NPs | In vitro: PC-12 cells | ↓αSN aggregating, ↓hazardous oligomers. | [186] | |
| Nanoformulations of Synthetic Drugs | |||||
| Levodopa | NPs | In vitro/ in vivo | ↓dyskinesia | [172] | |
| Bromocriptine | SLN based on a tristearin/tricaprin | In vitro | Controlled drug release by surrounding solid lipid barrier, firmly contained during the extended time established | [174] | |
| Chitosan | In vivo: Swiss albino mice | ↑absorption in the brain and protects catalepsy and akinesia | [171] | ||
| Ropinirole | PLGA | In vitro/ in vivo: male Wistar rats | ↓neurodegeneration | [175] | |
| PLN | In vitro/in vivo: male albino mice | ↓dose and dosing frequency, optimizing the therapeutic index, ↓side effects | [177] | ||
| Selegiline | NEs | In vitro: neuro-2a neuroblastoma cell line | ↑GSH, ↑SOD, ↓TBARS ↑drug bioavailability, ↑brain uptake, ↓decreased dopamine depletion | [181] | |
| NEs | In vivo: Wistar rats | ↓neurodamage caused by free radicals, ↓subsequent metabolic alterations | [182] | ||
| Apomorphine | SLNs | In vivo: male Wistar albino rats | ↑oral bioavailability, ↓dose, and frequency of administration, effectively targeted apomorphine to the brain striatum | [180] | |
| Pentamidine | Chitosan coated niosomes | In vivo: male C57Bl/6 J mice | ↓neuroinflammation, ↑dopaminergic neuronal function via blocking effect on glial-derived S100B function | [183] | |
| Pramipexole | Chitosan | In vivo: male Sprague-Dawley rats | Controlling motor deficits via its antioxidant potential, ↑SOD, ↑CAT, ↑ dopamine level in the brain | [178] | |
Abbreviations: ↑, increase or upregulation; ↓, decrease or downregulation; ASDs, amorphous solid dispersions; αSN, α-synuclein; APP, amyloid precursor protein; BACE, β-secretase; BDNF, brain-derived neurotrophic factor; bFGF, basic fibroblast growth factor; CAT, catalase; EGCG, epigallocatechin 3-gallate; MWCNTs, multiwalled carbon nanotubes; Lf-TMC NPs, lactoferrin-conjugated N-trimethylated chitosan nanoparticles; GMO, glyceryl monooleate; GSH, glutathione; iNOS, intrinsic nitric oxide synthase; lips@Fe3O4, Fe3O4 modified liposomes; MDA, malondialdehyde; MSCs, mesenchymal stem cells; NEs, nano emulsions; PS80-coated poly lactide NPs, polysorbate 80 coated poly(lactide) nanoparticles; NLCs, nanostructured lipid carriers; NP, nanoparticles; NPQ, nanoencapsulated quercetin; NSC, endogenous neural stem cells; PEI-HAS-NPs, polyethyleneimine-coated human serum albumin; PLGA-NPs, poly(lactide-co-glycolide nanoparticles; PLGA-PEG-B6, poly(lactide-co-glycolide)-block-poly(ethylene glycol)) conjugated with B6 peptide; SLNs, solid lipid nanoparticles; ROS, reactive oxygen species; SOD, superoxide dismutase; STL-PEG-PLGA, Solanum tuberosum lectin coupled polyethylene glycol-polylactide-polyglycolide.