Nanomedicine in the Management of Alzheimer’s Disease: State-of-the-Art
Abstract
:1. Introduction
2. Conventional Therapeutic Approaches and Their Limitations
3. Application of Nanomedicines in the Management of Alzheimer’s
4. Conclusions
5. Future Prospective
Author Contributions
Funding
Conflicts of Interest
References
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Topic | Information | References |
---|---|---|
Alzheimer’s disease (AD) | Progressive neurological condition that causes irreversible dementia syndrome. Incidence increases with age: currently affects 32.6 million people worldwide. Expected to reach 78 million by 2030 and 139 million by 2050 without new treatments. | [1,4] |
Pathology of AD | Caused by extracellular aggregation of amyloid beta (Aβ) plaques and accumulation of intraneuronal neurofibrillary tangles of tau (τ) protein | [7] |
Risk factors for AD | Associated with cardiovascular risk factors such as hypertension, diabetes, atherogenic dyslipidaemia, and obesity—environmental exposure to toxicants, genetic factors, mutation, trauma, and metabolic diseases can also cause AD. | [8,9] |
Blood–brain barrier (BBB) | It is one of the most challenging physiological barriers. The drug movement in the brain parenchyma is obstructed by a physical interface, the BBB, present between the central nervous system (CNS) and peripheral circulation. Lipophilic molecules smaller than 400 Da can cross the BBB. | [12] |
Conventional treatment of AD | Non-pharmacological and pharmacological approaches: Non-pharmacological approaches such as sleep, physical activity, and music therapy can also help. Symptomatic treatment with NMDA receptor antagonists and cholinesterase inhibitors (CHEIs) are common pharmacological approaches. | [20] |
Food and Drug Administration (FDA)-approved drugs for AD | Aduhelm (aducanumab-avwa), Aricept (donepezil hydrochloride), Excelon patch (rivastigmine transdermal system), Namenda (memantine HCl), Namzaric (memantine hydrochloride extended-release + donepezil hydrochloride), and Razadyne (galantamine hydrobromide). | [21,22] |
Current treatments for AD | Only reduce symptoms. Temporarily enhance cognitive abilities. Lack brain specialization and cause adverse effects. | [22] |
Limitations of conventional treatment | First-pass metabolism and unfavorable pharmacokinetics—lower bioavailability and high dosage requirements. Physicochemical properties can affect drug effectiveness: bioactives may have suboptimal therapeutic effects via the oral route. | [23,24] |
Nanotechnology and AD | Nanotechnology can aid in early detection and drug development for AD. Nanocarriers have advantages over conventional treatment. Drug-loaded nanocarriers can improve drug delivery to the brain across the BBB. Further details are described in Table 2. | [25] |
Drugs | Nanocarriers | Outcomes/Benefits | References |
---|---|---|---|
DPL | Liposome | Donepezil via oral drug delivery cannot cross BBB. Donepezil-loaded liposome are made and intranasally administered to rapidly cross the BBB and shows improved bioavailability and reduces the systemic toxicity of it against AD. | [15] |
A oligomer-specific scFv-AbW20 | superparamagnetic iron oxide NPs (SPIONs) | This study found have promise results against AD and exceptional early diagnostic potential. | [32] |
Silicon dioxide | Silicon nanoparticle | Significantly induced cellular apoptosis, elevate the level of intracellular ROS in dose-dependent manner, decrease the cell viability, enhanced phosphorylation of tau at Ser262 and Ser396. | [33] |
Sialic acid | Selenium (Se)-NPs | The loading of Sialic acid into Se-NPs increase the permeation through BBB and reduces the aggregation of Aβ in the animal model of AD. | [36] |
Curcumin | Selenium NPs encapsulated into PLGA nanospheres | This study found strong inhibition against Aβ aggregation and can be used as targeted drug delivery in treating AD. | [37] |
Triphenyl phosphonium | Cerium nanoparticles | TPP-ceria NPs effectively penetrate mitochondria to scavenge ROS to reduce oxidative stress. | [38] |
Donepezil (DPL) | SLNs | Intranasal administration of DP-SLNs significantly increase the concentration of drug in brain over the i.v. administration of DPL solution. Further, the scintigraphy study observed localization of DPL-SLNs into the rabbit’s brain. | [43] |
Pomegranate extract | LNPs | This study found higher antioxidant effects and decreased NFTs and Aβ deposition in the aluminium chloride-induced rat model of AD. | [45] |
α-Bisabolol | LNPs | Protect the neuro-2a cells from inhibited Aβ aggregation and Aβ induced neurotoxicity | [46] |
Erythropoietin (EPO) | Solid lipid nanoparticles (SLNs) | Erythropoietin (EPO) helps neuronal survival and regulates AD, but very limited BBB permeation, due to hydrophilicity and high molecular weight and rapid clearance from the blood stream. EPO-encapsulated SLNs overcomes abovementioned issues and decrease oxidative stress and Aβ deposition and show increased spatial memory. | [47] |
Curcumin | NLCs | This study found enhanced curcumin bioavailability in the brain and reduces the hallmark of Aβ in AD | [51] |
Curcumin | SLNs | The study found to reduces the behavioural dysfunction and reverses several neurotransmitters into the brain against animal model of AD. | [55] |
Curcumin | Liposomes | It can deliver the drug to CNS, permeate the BBB, and show better anti-Alzheimer’s effect in animal model. | [56] |
Indomethacin (Ind) | Lipid nano capsules (LNCs) | This study has been investigated that Ind loaded LNCs inhibit neuroinflammation induced by Aβ1-42 in organotypic hippocampal cultures and decrease A-induced cell death in AD animal model | [57] |
Vitamin D | PLGA-NPs | Vitamin D observed neuroprotective effect, but poor solubility and bioavailability. The vitamin D loaded PLGA-NPs studied on murine AD model, results to decreased neuronal apoptosis and enhanced cognitive function was observed. | [60] |
Huperzine A | PLGA-NPs | Huperzine A was loaded into PLGA-NP conjugated with lactoferrin, showed enhanced release kinetics, and significantly decreased AD symptoms. | [61] |
Memantine | Polymer-based NPs (PBNPs) | Memantine loaded PBNPs shows effective an anti-inflammatory and anti-Alzheimer’s effect against AD animal model. | [62] |
Zinc and sitagliptin | PBNPs | It shows improved cognitive dysfunction and reduced neuroinflammation when studied for their anti-Alzheimer effect against AD animal model. | [63] |
Thymoquinone (TQ) | PLGA-NPs | TQ-containing PLGA NPs with polysorbate-80 (P-80) could be a safe and effective way to transport NPs across the BBB and into the brain. The PLGA-NPs are shielded from being opsonized and cleared by the body because of the P-80 surfactant coating. TQ works by reducing the production of superoxide radicals primarily through blocking the enzyme xanthine-oxidase. | [66] |
Tacrine | Dendrimers with a poly (propylene imine) core and a maltose histidine shell (G4HisMal) | Tacrine loaded into generation 4.0 and PAMAM dendrimers has been employed and has improved biocompatibility and reduced the toxicity of the drug used to treat the AD. | [68] |
Osthole (Coumarin derivative) | Liposome | This study found increased intracellular uptake by APP-SH-SY5Y cells and exerted a cytoprotective effect. Prolonged the cycle time and elevate the accumulation of Osthole in the brain | [69] |
Rivastigmine | Liposome | Increase the concentration and exposure in the brain. | [70] |
Ligustrazine phosphate | Ethosome | Drug penetration and deposition significantly higher over the plain drug. | [71] |
Morin hydrate | ME | The morin hydrate solution given by a parenteral route has several drawbacks, such as safety issues, low patient compliance, and expensive medication. Avoiding the BBB, intranasal delivery of morin hydrate-loaded ME is a potential strategy, and it offers an advantage as it is non-invasive. | [72] |
Ibuprofen | Microemulsion (ME) | A novel repurposing strategy and route of administration are presented in this study for the treatment of AD. The in vivo result in rats found uptake of a novel ibuprofen loaded ME nearly four times higher than that of the intravenous and ten times than that of the oral administrations. | [73] |
Tacrine | ME | The intranasal administration of tacrine-loaded ME results in the quickest memory recovery in scopolamine-induced amnesic mice. | [74] |
Huperzine A | ME | Huperzine A loaded ME improves cognitive function in mice compared to oral suspension. | [75] |
Naringenin | Nanoemulsion | The study outcome shows that nanoemulsion of naringenin could be used to overcome Aβ neurotoxicity and amyloid genesis. | [76] |
Memantine | Nanoemulsion | Memantine loaded nanoemulsion using homogenization and ultrasonication was studied for its anti-Alzheimer effect. It was given by intranasal route. This nanoemulsion crosses the BBB and increases the anti-AD effect compared with the conventional dosage form. | [77] |
DPL | Nanoemulsion | Using labrasol and glycerol at a concentration of 10% w/w, a nanoemulsion containing donepezil hydrochloride was developed. Donepezil hydrochloride nanoemulsion has the potential to treat AD, due to its antioxidant and radical scavenging effects. | [78] |
Deferoxamine | Nanoemulsion gel | Deferoxamine delivered via nanogels made of chitosan and tripolyphosphate shows an effective therapeutic action against AD. | [79] |
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Mir Najib Ullah, S.N.; Afzal, O.; Altamimi, A.S.A.; Ather, H.; Sultana, S.; Almalki, W.H.; Bharti, P.; Sahoo, A.; Dwivedi, K.; Khan, G.; et al. Nanomedicine in the Management of Alzheimer’s Disease: State-of-the-Art. Biomedicines 2023, 11, 1752. https://doi.org/10.3390/biomedicines11061752
Mir Najib Ullah SN, Afzal O, Altamimi ASA, Ather H, Sultana S, Almalki WH, Bharti P, Sahoo A, Dwivedi K, Khan G, et al. Nanomedicine in the Management of Alzheimer’s Disease: State-of-the-Art. Biomedicines. 2023; 11(6):1752. https://doi.org/10.3390/biomedicines11061752
Chicago/Turabian StyleMir Najib Ullah, Shehla Nasar, Obaid Afzal, Abdulmalik Saleh Alfawaz Altamimi, Hissana Ather, Shaheen Sultana, Waleed H. Almalki, Pragya Bharti, Ankit Sahoo, Khusbu Dwivedi, Gyas Khan, and et al. 2023. "Nanomedicine in the Management of Alzheimer’s Disease: State-of-the-Art" Biomedicines 11, no. 6: 1752. https://doi.org/10.3390/biomedicines11061752