Recent Advances in the Treatment of Alzheimer’s Disease Using Nanoparticle-Based Drug Delivery Systems
Abstract
:1. Introduction
2. AD Pathology
2.1. Cholinergic Deficit
2.2. Amyloid Hypothesis
2.3. Tau Hypothesis
2.4. Oxidative Stress
2.5. Cellular and Vascular Dysfunction
2.6. Cholesterol
2.7. Inflammation
2.8. Metal Imbalance
3. Commercially Available Medicines and Those in Pipelines
4. BBB Physiology and Structure
5. Strategies to Overcome the BBB
5.1. Crossing the BBB
5.2. Avoiding the BBB
5.3. Disrupting the BBB
6. NP-Based Delivery System for the Treatment of AD
6.1. Liposomes
6.2. Micelles
6.3. Solid Lipid NPs (SLNs)
6.4. Polymeric NPs (PNPs)
6.5. Dendrimers
6.6. Nanoemulsions (NEs)
6.7. Inorganic NPs
7. Immunotherapy for AD
8. Future Perspectives and Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Drugs | Trade Name (Company) | Action Mechanism | Dosage Form | Dose | LogP (Permeability) Molecular Weight (M.W) (g/mol) | K (Partition Coefficient) |
---|---|---|---|---|---|---|
Tacrine | Cognex (Sciele, Atlanta, GA, USA) | Reversible inhibition of acetylcholinesterase (AChE) | Capsule | Initial dose: 10 mg orally q.i.d (between meals if possible) for 6 weeks. Maintenance dose: may increase to 20 mg orally q.i.d. Further increases to 120 mg and 160 mg/day may be done in 6-week intervals. | 2.71 M.W = 234.72 | |
Donepezil | Aricept (Pfizer, New York City, NY, USA) | Reversible inhibitor of acetylcholinesterase which prevents the hydrolysis of acetylcholine. | Tablet | 5 mg q.d., may increase to 10 mg/day after 4–6 weeks if tolerated, then to 23 mg/day after at least 3 months | 4.7 M.W = 379.5 | log Kow = 4.86 (est) |
Rivastigmine | Exelon (Novartis, Basel, Switzerland) | Inhibits the hydrolytic activity of AChE and BChE and binds to catalytic sites. | Solution Capsule | Oral Solution and capsules 6 mg to 12 mg per day, administered b.i.d. (daily doses of 3 mg to 6 mg b.i.d.) | 2.3 M.W = 250.34 | |
Galantamine | Razadyne (Janssen, Beerse, Belgium) | Binds reversibly to acetylcholine esterase and enhances the intrinsic action of acetylcholine on nicotinic receptors. | Tablet Capsule Oral solution | Tablets contain 4 mg, 8 mg, and 12 mg galantamine. Capsules contain 8 mg, 16 mg, and 24 mg galantamine. Oral solution contains 4 mg galantamine (as 5.13 mg galantamine hydrobromide) per mL. | 1.8 M.W = 287.35 | |
Memantine | Namenda (Allergan, Dublin, Ireland) | N-methyl D-aspartate (NMDA) antagonist | Tablet Oral solution | Tablets: 5 mg q.d., may increase to 10 mg/day, 15 mg/day, and 20 mg/day at 1-week intervals if tolerated Oral solution: same as above | 3.28 M.W = 179.3 | log Kow = 3.28 |
Memantine and Donepezil | Namzaric (Actavis, Parsippany, NJ, USA) | N-methyl D-aspartate (NMDA) antagonist plus cholinesterase inhibitor | Capsule (ER) | 7 mg memantine/10 mg donepezil q.d., may increase to 28 mg memantine/10 mg donepezil in 7 mg increments at 1-week intervals if tolerated | M.W = 215.76 | |
Aducanumab | Aduhelm (Biogen, Cambridge, MA, USA) | Targets accumulated Aβ plaques | Intravenous infusion | Doses 1 and 2 (weeks 0 and 4)—1 mg/kg IV over one hour Doses 3 and 4 (weeks 8 and 16—3 mg/kg IV over one hour | M.W = 145,912.34 |
Drug | Mechanism of Action | Therapeutic Purpose | Stage of AD | Target | Phase | Sponsor | Start Estimated End Dates | |
---|---|---|---|---|---|---|---|---|
Disease-Modifying Biologics | ||||||||
New Therapeutics | Aducanumab | Disrupts Aβ plaques and oligomers | DMT | Mild to moderate | Amyloid | 3 | Biogen, Cambridge, MA, USA | Mar 2020 Oct 2023 |
Gantenerumab | Monoclonal antibody acts at Aβ plaques and oligomers | DMT | Mild to moderate | Amyloid | 2 | Roche, Basel, Switzerland | Dec 2020 Feb 2024 | |
Pepinemab | Monoclonal antibody directed at semaphoring 4D to reduce inflammation | DMT | Mild | Inflammation | 1 | Vaccinex. Inc., Rochester, NY, USA | Jul 2021 Jan 2023 | |
LY3372689 | Tau protein aggregation inhibitor | DMT | Moderate | Tau | 2 | Eli Lilly & Company, Indianapolis, IN, USA | Sep 2021 Jun 2024 | |
TRx0237 | Inhibition of tau protein aggregation | DMT | Mild to moderate | Tau | 3 | TauRx Therapeutics, Aberdeen, Scotland | Jan 2018 Jun 2023 | |
Disease-Modifying Small Molecules | ||||||||
Sumifilam | Alters conformation of filamin A | DMT | Mild to moderate | Filamin A | 2 | Cassava Sciences, Inc, Austin, TX, USA | Nov 2021 Oct 2023 | |
Tricaprilin (contains caprylic acid triglyceride) | Induces ketosis and improves mitochondrial and neuronal function | DMT | Mild to moderate | Metabolism and bioenergetics | 3 | Cerecin, Anson Road, Singapore | Jan 2021 Feb 2023 | |
Symptoms-Reducing Small Molecules | ||||||||
AD-35 | Acetylcholinesterase inhibitor | Cognitive enhancer | Mild to moderate | Neurotransmitter receptors | 2 | Zhejiang Hisun Pharmaceutical, Jiaojiang District, Taizhou, China | Dec 2018 July 2021 | |
Disease-Modifying Biologics | ||||||||
Repositioned Drugs | BCG vaccine | Vaccination against tuberculosis infection; immunomodulator | DMT | - | Inflammation/immunity | 2 | Mindful Diagnostics and Therapeutics, Eau Claire, WI, USA | Nov 2020 Dec 2021 |
IVIG (NewGam 10%) | Polyclonal antibody | DMT | Mild | Amyloid | 2 | Sutter Health, Sacramento, CA, USA | Jan 2011 Dec 2019 | |
Disease-Modifying Small Molecules | ||||||||
Losartan & amlodipine & atorvastatin + exercise | Angiotensin II receptor blocker (losartan), calcium channel blocker (amlodipine), cholesterol agent (atorvastatin) | DMT | - | Vasculature | 3 | University of Texas Southwestern, Houston, TX, USA | Feb 2017 Mar 2022 | |
Metformin | Sensitize insulin to improve metabolism of CNS glucose | DMT | Mild | Metabolism and bioenergetics | 3 | Columbia University, NIA, NY, USA | Jan 2021 Apr 2024 | |
Montelukast | Leukotriene receptor antagonist | DMT | Mild to moderate | Inflammation | 2 | Emory University, Atlanta, GA, USA | Sep 2019 Oct 2022 | |
Hydralazine | Antioxidant | DMT | Mild to moderate | Oxidative stress | 3 | Shahid Sadoughi University of Medical Sciences and Health services, Yazd, Iran | Jun 2021 Jun 2023 | |
Suvorexant | Dual orexin receptor antagonist; improves sleep with effects on CSF Aβ | DMT | - | Neurotransmitter receptors | 2 | Washington University School of Medicine, St. Louis, MO, USA | Jan 2021 Jan 2025 | |
Trehalose | Induces autophagy and promotes clearance of aggregated proteins | DMT | Mild to moderate | Cell death | 1 | Mashhad University of Medical Sciences, Mashhad, Razavi Khorasan, Iran | Aug 2020 Aug 2022 | |
Vorinostat | Histone deacetylase (HDAC) inhibitor; enhanced synaptic plasticity | DMT | Mild | Epigenetics | 1 | German Center of Neurodegenrative Disease (DZNE), Bonn, Germany | Sep 2017 Mar 2022 | |
Symptoms-Reducing Small Molecules | ||||||||
Caffeine | Pleiotropic effect on CNS function | Cognitive Enhancer | Mild | Metabolism and bioenergetics | 3 | University Hospital, Lille, France | Nov 2021 Nov 2024 | |
Escitalopram | Selective serotonin reuptake inhibitor | Neuropsychiatric symptoms | Mild | Neurotransmitter receptors | 3 | Johns Hopkins University, NIA, Baltimore, MD, USA | Jan 2018 Aug 2022 | |
Nabilone | Synthetic cannabinoid; antiemetic | Neuropsychiatric symptoms (agitation) | Mild to moderate | Neurotransmitter receptors | 3 | Sunnybrook Health Sciences Center, ADDF, Torinto, ON, Canada | Feb 2021 Oct 2025 | |
Nicotine | Nicotinic acetylcholine receptor agonist | Cognitive enhancer | Mild | Neurotransmitter receptors | 2 | University of Southern, California, NIA, ATRI, Vanderbilt University, Nashville, TN, USA | Jan 2017 July 2023 | |
Prazosin | α-1 adrenoreceptor antagonist | Neuropsychiatric symptoms (agitation) | Mild to moderate | Neurotransmitter receptors | 2 | ADCS, NIA, Maitland, FL, USA | Oct 2018 Dec 2022 | |
Riluzole | Glutamate modulator agent | Cognitive enhancer | Mild | Neurotransmitter receptors | 2 | Icahn School of Medicine at Mount Sinai, NY city, NY, USA | Completed | |
Sargramostim | Recombinant human GM-CSF | Cognitive enhancer | Mild to moderate | Metabolism and bioenergetics | 2 | University of Colorado, Denver, USA | Dec 2021 Jul 2024 | |
THC-free CBD oil | Cannabinoid with effects on cannabinoid receptors | Neuropsychiatric symptoms agents (agitation) | Severe | Neurotransmitter receptors | 2 | Eastern Virgina Medical School, Norfolk, VA, USA | Feb 2021 Jun 2022 |
Influx Transporters | Efflux Transporters | Receptor Transporters |
---|---|---|
Choline transporter (ChT) | Peptide transport system-6 (PTs-6) | Insulin receptors (IR) |
Sodium-coupled glucose transporters (SGLTs) | Breast cancer resistant protein (BCRP) | Insulin-like growth factor receptor (IGFR) |
Cationic amino acid transporter (CAT1) | P-glycoprotein (P-gp) | Transferrin receptors (TfR) |
1-type large amino-acid transporter (LAT1) Excitatory amino-acid transporters (EAATs) | Leptin receptor (LepR) | |
Glucose transporter (GLUT1) (GLUT3) | Low-density lipoprotein receptor (LDLR) | |
Monocarboxylate lactate transporter (MCT1) Receptor for glycation end products (RAGE) | Neonatal Fc receptor (FcRN) | |
Lactoferrin receptor (LR) |
Drug | Carrier Material | Ligand | Particle Size (nm) | Zeta Potential (mV) | Route of Administration, Dose | In Vitro/In Vivo Model | Outcome | Reference |
---|---|---|---|---|---|---|---|---|
Liposome | ||||||||
Metformin | Phosphatidyl serine | - | 145 | −41 | Intraperitoneal, 50 mg/kg | Adult male Wistar rats | in vivo: Decreased neuroinflammation. Enhanced cognition restoration. | [112] |
- | Chitosan | pApoE2 | 167.8 ± 2.47 | 19.8 ± 3.6 | Intravenous, 1 mg/kg | bEnd.3 cells C57BL/6 mice | in vitro: Decreased cell viability in all cell lines. Increased concentration of phospholipid. in vivo: Approximately 2 times higher ApoE protein expression than endogenous ApoE levels. | [111] |
Osthole | - | Transferrin | 104.28 ± 3.76 | −6.95 ± 0.56 | Tail vein intravenous, 10 mg/kg | hCMEC/D3 cells and APP-SH-SY5Y cells APP/PS-transgenic mice | in vitro/in vivo: pH-controlled release up to 72 h. Enhanced penetration and drug accumulation. | [114] |
GSH-PEG | VHH-pa2H Glutathione (GSH) | 108 | IV bolus injection, 5 mg/kg | APPswe/PS1dE9 transgenic mice | in vivo: Increased standard uptake values (SUV) of VHH-pa2H in the blood. | [113] | ||
Galantamine HBr | Soya Phosphatidylcholine | - | 112 ± 8 | −49.2 ± 0.7 | Oral and intranasal, 3 mg/kg | PC-12 cell, male SD rats | in vitro: Reduced cytotoxicity Enhanced BBB penetration. in vivo: More bioavailability in brain. Enhanced efficacy. | [107] |
Donepezil | 1,2-distearyl-sn-glycero-3-phospholine (DSPC) | - | 102 ± 3.3 | −28.31 ± 0.85 | Oral and intranasal, 1 mg/kg | Male Wistar rats | in vitro: 75.5% drug release in 8 h. in vivo: Enhanced penetration. Enhanced bioavailability. | [109] |
Rivastigmine | EPC, Cholesterol, DSPE-PEG-CPP | CPP | 178.9 | −8.6 ± 2.4 | Intranasal and intravenous, 1 mg/kg | Endothelial cells, male SD rats | in vitro High encapsulation efficiency. Sustained-release behavior. in vivo IN route shows more activity | [108] |
Micelles | ||||||||
Resveratrol | PEG-PLA | C3 peptide | 43.85 ± 0.94 | 12.9 ± 0.17 | Intravenous, 10 mg/kg | HT22 cells, APP/PS1 transgenic mice | in vitro: Improvement on brain accumulation and increased targeting. in vivo: Enhance cognitive performance. Inhibited Aβ aggregation. Enhanced activity. | [118] |
Curcumin | PEG | Aβ peptide | 65 | Intravenous | SH-SY5Y, APPswe/PS1dE9 transgenic mice | in vitro/in vivo: Increased efficacy. Inhibited Aβ aggregation. Improved memory behavior. | [120] | |
- | Linoleic acid | Lactoferrin | 120 ± 12.4 | −32.8 ± 3.66 | Oral, 4 gm/mL | Adult male Wistar rats | in vitro/in vivo Enhanced cognition Reduced oxidative stress. Reduced Aβ aggregation. | [121] |
PMO-b-PBM, POEG-b-PBM and PF | - | 70 | - | PC-12 cells | in vitro: Reduced Aβ aggregation. Reduced Aβ fibrillation-induced cytotoxicity. | [122] | ||
Solid–lipid NPs | ||||||||
galantamine HBr | Glyceryl behnate, pluronic F-127, tween 80 | - | 88 ± 1.89 | −18.75 ± 1.7 | Oral route, 2.5 mg/kg | Adult Wistar rats | in vitro: Maximum drug entrapment. Drug release > 90% for a period of 24 h. in vivo: Enhanced bioavailability 2-fold Memory restoration. | [123] |
Rivastigmine | Campritol 888 ATO | - | 82.5 ± 4.07 | 3.20 ± 1.44 | - | Franz diffusion cell, goat nasal mucosa | in vitro: Higher diffusion with SLN. Ex-vivo: Maximum diffusion was seen with up to 8 h. | [124] |
Donepezil | Stearic acid, oleic acid, lecithin, sodium taurodeoxytaurocholate | - | 177.05 ± 2.12 | −55.35 | Transdermal | - | in vitro: Increased drug skin permeation. Enhanced drug delivery. | [126] |
Rivastigmine | GMS, castor oil | - | 134.5 ± 15.1 | −11.8 ± 2.24 | Transdermal | Albino Wistar rats | in vitro/in vivo: Non-irritant. Enhanced bioavailability. | [125] |
Erythropoietin | GMS, span 60, span 80, tween 80 | - | 219.9 ± 15.6 | −22.4 ± 0.8 | Intraperitoneal, 1250 IU/kg and 2500 IU/kg | Albino male Wistar rats | in vitro: 39% of EPO released in first 3 h followed by approximately 90% for 72 h. in vivo: Improved memory dysfunction. Enhanced efficacy. | [127] |
Nicotinamide | Stearic acid, phospholipon 90G, sodium taurocholate | Phosphatidylserine | 124 ± 0.8 | −46.1 ± 0.65 | Intravenous or intraperitoneal | BCES, SH-SY5Y, adult male Sprague-Dawley rats | in vitro: Enhanced BBB penetration. in vivo: Neuroprotective potential Improved cognition impairment. | [128] |
Resveratrol | Lecithin | - | 286 ± 1.47 | −17.5 ± 0.23 | Oral, 10 mg/kg | Male Sprague-Dawley rats | in vitro: 91% sustained release after 24 h. in vivo: 4.5 times bioavailability in brain. Effective antioxidant activity. | [129] |
Resveratrol and grape extract | Cetyl palmitate, tween 80, tween 20 | Anti-transferrin receptor mAb (OX26 mAb) | 254 ± 17 | −4.0 ± 0.1 | - | HBEC | in vitro: Efficient cellular uptake. Inhibited Aβ aggregation. | [130] |
Quercetin | - | - | 152 | −20.7 | Intravenous, 4.41 mg/kg | Male Wistar rats | in vitro/in vivo: 85.73% Drug entrapment efficiency. Effective in crossing BBB. Improvement in memory. | [132] |
Lipid NPs | ||||||||
Quercetin | - | Transferrin | 219 ± 13 | −28 ± 2 | - | hCMEC/D3 cells | in vitro: 80–90% of entrapment efficiency Minimum cytotoxicity at BBB cell line. | [131] |
Curcumin | PC, cholesterol oleate, glycerol trioleate | Lactoferrin | 103.8 ± 0.6 | −5.80 ± 0.73 | Intravenous, 10 mg/kg | BCECs, SD rats | in vitro/in vivo: Effective BBB penetration. Long-term leads to enhanced activity. | [133] |
Polymeric-NPs | ||||||||
Galantamine | PLA-PLGA | - | 198.00 ± 0.02 | −27.42 ± 0.03 | Intranasal, 3 mg/kg | Wistar rats | in vitro/in vivo: Good stability between NP and drug. More bioavailability in the brain. | [137] |
Donepezil | PEG-PLGA | - | 174 ± 12 | −20.45 | - | HBMEC and HA cell | in vitro: High destabilizing effect on fibril formation. Decreased neuroinflammation. | [136] |
Rivastigmine | L-Lactide-depsipeptide | - | 142.2 ± 21.3 | - | - | in vitro: Entrapment efficiency of 60.72 ± 3.72% was obtained. Showed sustained release with 90% of drug for up to 72 h. | [138] | |
Resveratrol | Methoxy PEG, -caprolactone | - | 80.70 ± 7.12 | ~0 mV | - | Caenorhabditis elegans, N2, CF1553, CL4176, and CL1175 | in vitro/in vivo: Enhanced antioxidant properties. Enhanced radical scavenging. Enhanced anti-lipid peroxidation. | [139] |
Curcumin | PLGA-PEG | B6 peptide | ~100 | 3.83 ± 0.89 | Intraperitoneal, 25 mg/kg | HT22 cells/APP/PS1 transgenic mice | in vitro: Enhanced cellular uptake. Possessed good blood compatibility in vivo: Improvement in spatial learning and memory. Ex-vivo: Reduced Aβ aggregation. | [140] |
ECG | PLGA, PEG, ascorbic acid, tween 80 | - | 124.8 ± 5.2 | −15 | Oral, 40 mg/kg | BMVECs, APP/PS1, C57BL/6 mice | in vitro: Effective in crossing BBB. in vivo: Reduced neuroinflammation. Enhance spatial learning and memory. | [142] |
Pioglitazone | PLGA-PEG, tween 80 | Anti-Aβ antibody | 155.0 ± 1.8 | −13.0 ± 0.5 | Oral, 10 mg/kg | HBEC,hCMEC/D3 cell line, APP/PS1 transgenic mice | in vitro: Better BBB penetration. in vivo: Reduced Aβ peptide in brain. Improved memory defect. | [143] |
Quercetin | PLGA, PVA | - | 150 | Intravenous, 20 mg/kg | SH-SY5Y cells, APP/PS1 mice, BALB/c nude mice | in vitro/in vivo: Low cellular toxicity. High cell viability. Inhibited neurotoxicity. Enhanced cognition and memory. | [144] | |
- | PEG-PLA | B6 peptide | 118.3 ± 7.8 | −22.65 ± 0.85 | Intravenous, 1 mg/kg | bEnd.3 cells, male ICR mice | in vitro: Enhanced brain penetration. in vivo: Enhanced cognition. | [141] |
Galantamine | Thiolated-chitosan NPs | - | 149.3 | 27.2 | Intranasal 4 mg/kg | Swiss albino mice | in vivo: Effective acetylcholinesterase activity. | [146] |
Memantine | PAMAM (dendrimer) | Lactoferrin | 131.72 ± 4.73 | 20.13 ± 0.94 | Intraperitoneally, 2 mg/kg | Swiss albino mice | in vitro: PAMAM-MEM maximum release concentration was 77.14 ± 6.0% after 6 h. in vivo: Improvement in behavioral responses. Enhanced acetylcholinesterase (AChE) activity. | [148] |
Nanoemulsions | ||||||||
Memantine | - | - | ~11 | −19.6 | Intranasal, 5 mg/kg | Neuro 2a, Sprague-Dawley rats | in vitro/in vivo: 98% cell viability and sustained its antioxidative potential. Increased bioavailability. | [154] |
Donepezil | Labrasol (10%) as oil, CPC (1%) as surfactant in water (80%), glycerol (10%) as co-surfactant | 65.36 | −10.7 | Intranasal, 0.45 mg/kg | Neuro 2a, Sprague-Dawley rats | in vitro/in vivo: Maximum drug release of 99.22% in 4 h in PBS. Non-toxic Effective drug delivery. | [155] | |
Huperazine A | Capryol 90 (oil phase), cremophor EL & labrasol (surfactant & co-surfactant) & lactoferrin (targeting ligand) | Lactoferrin | 16.75 ± 0.4 | 5.67 ± 0.39 | Intranasal | hCMEC/D3 cells, adult Wistar rats | in vitro/in vivo: No nasal mucosal toxicity. Effective BBB penetration. Enhanced activity. | [156] |
Quantum Dots | ||||||||
- | Graphene QDs | - | 10 ± 1.3 | −40 ± 0.4 | - | Adult male Wistar rats | in vitro/in vivo: Enhanced penetration across BBB. Improved learning and memory. Reduced level of lipid peroxide and nitric oxide. | [158] |
- | Black phosphorous QDs | - | ~3 | - | PC12 cells | in vitro: Low cell toxicity. Inhibited insulin and Aβ aggregation. | [159] | |
- | Selenium-doped carbon QD | - | ~25 | Intravenous | PC12 cells, adult male Wistar rats | in vitro/in vivo: High cell viability. Inhibited Aβ aggregation. Improved memory and cognitive function of an AD rat model. | [160] | |
Curcumin | Graphene QD & indium-tin-oxide Electrode | - | ~8 | - | - | in vitro: High sensitivity on detection of ApoE4 DNA. Enhanced efficacy. | [161] | |
Gold nanoparticles | ||||||||
- | - | L and D glutathione | 4 | Intravenous, 25 mg/kg | SH-SY5Y cells, C57BL/6 mice | in vitro/in vivo: Effective BBB penetration. Improved behavioral performance. | [162] | |
AuNP | - | - | 20 | Intraperitoneal, 2.5 mg/kg | Male Wistar rats | in vivo: Normalize Tau phosphorylation. Prevented oxidative stress and neuroinflammation. | [163] | |
AuNP | - | Bucladesine | 5 | −47.7 ± 10.9 | Intrahippocampal, intraperitoneal | Male Wistar rats | in vivo: Better acquisition and retention of spatial learning and memory. Improved neuron survival. | [164] |
- | 3D-Au-PAMAM, electro grafted PABA | CAb-GA conjugate | - | - | Detection: Effective detection of tau protein. LOD value of 1.7 pg/mL. | [165] | ||
Magnetic Nanoparticles | ||||||||
Quercetin | SPIONs | - | 50 | Oral, 50 and 100 mg/kg | Male Wistar rats | in vivo: Increased penetration. Enhanced Bioavailability. | [167] | |
- | Sialic acid (SA)-modified selenium (Se) NPs | B6 peptide | 95 | −14.4 | - | PC12 cells and bEnd.3 cells | in vitro: Effective in crossing BBB. Inhibitory effects on Aβ peptide. | [170] |
siRNA | PEGylated magnetite NPs | OmpA | 10 | - | HFF-1 cells and SH-SY5Y cells | in vitro: Reduced cell toxicity. Enhanced activity. Silencing of BACE1 gene in HFF-1 cells. | [171] |
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Poudel, P.; Park, S. Recent Advances in the Treatment of Alzheimer’s Disease Using Nanoparticle-Based Drug Delivery Systems. Pharmaceutics 2022, 14, 835. https://doi.org/10.3390/pharmaceutics14040835
Poudel P, Park S. Recent Advances in the Treatment of Alzheimer’s Disease Using Nanoparticle-Based Drug Delivery Systems. Pharmaceutics. 2022; 14(4):835. https://doi.org/10.3390/pharmaceutics14040835
Chicago/Turabian StylePoudel, Prashant, and Soyeun Park. 2022. "Recent Advances in the Treatment of Alzheimer’s Disease Using Nanoparticle-Based Drug Delivery Systems" Pharmaceutics 14, no. 4: 835. https://doi.org/10.3390/pharmaceutics14040835
APA StylePoudel, P., & Park, S. (2022). Recent Advances in the Treatment of Alzheimer’s Disease Using Nanoparticle-Based Drug Delivery Systems. Pharmaceutics, 14(4), 835. https://doi.org/10.3390/pharmaceutics14040835