Nanoparticles for the treatment of the alzheimer’s disease

review article

Authors

  • Luísa Cruz Lopes Instituto Politécnico de Viseu, Escola Superior de Tecnologia e Gestão de Viseu, CERNAS, Viseu, Portugal https://orcid.org/0000-0001-6502-7202
  • Ana Lopes Escola Secundária Viriato, Viseu, Portugal
  • Maria Escudeiro Universidade do Porto, Instituto de Ciências Biomédicas Abel Salazar, Porto, Portugal
  • Cláudia Duarte Instituto Politécnico de Viseu, 3504-510 Viseu, Portugal https://orcid.org/0000-0001-9126-4623
  • Rafaela Ferreira Instituto Politécnico de Viseu, 3504-510 Viseu, Portugal
  • Francisco Graça Instituto Politécnico de Viseu, 3504-510 Viseu, Portugal https://orcid.org/0000-0002-0241-3365
  • Isaura Silva Instituto Politécnico de Viseu, 3504-510 Viseu, Portugal
  • Bruno Esteves Instituto Politécnico de Viseu, Escola Superior de Tecnologia e Gestão de Viseu, CERNAS, Viseu, Portugal https://orcid.org/0000-0001-6660-3128

DOI:

https://doi.org/10.29352/mill0210e.26245

Keywords:

alzheimer's disease, nanomaterials, plga, nanotechnology, toxicity

Abstract

Introduction: Alzheimer's Disease is a primary neurodegenerative pathology of unknown etiology and influenced by several factors with characteristic neuropathological and neurochemical features. Currently, drugs approved for the treatment of this disease only allow to relieve symptoms and are accompanied by several side effects. Nanotechnology appears as an alternative for the treatment of Alzheimer's, as it offers many advantages to modern medicine allowing a non-invasive and targeted diagnosis and treatment, reducing adverse reactions and systemic effects.

Objective: The article aims to recognize the potential of using nanoparticles in the treatment of Alzheimer's Disease, identifying the most promising treatments and their possible side effects.

Methods: A narrative bibliographic review based on consulting databases such as Science Direct, Web of Science, PubMed and Scielo.

Results: Gold nanoparticles are capable of crossing BHE, carrying essential drugs to inhibit the aggregation of Aβ peptides, as well as dissolve pre-existing fibrilla. Biodegradable and biocompatible polymers, such as polyglycolic polylactide (PLGA), are a promising and safe approach and have been widely used. The best techniques are those that guarantee that nanoparticles are capable of crossing the BHE, reach their therapeutic target, as well as guarantee that these particles do not induce toxic effects in the body. Although nanoparticles are able to treat some diseases efficiently, little is known about their side effects, they may or may not be more harmful to the body than the disease they intended to treat.

Conclusion: There are several promising therapeutic approaches, but none has yet been approved, since it is difficult to maintain adequate drug concentrations in the intraneuronal space. Establishing the toxic dose is necessary for the approved use of a nanoparticle in a treatment, but it is almost impossible to predict its cytotoxic effects in extraneuronal regions.

Downloads

Download data is not yet available.

References

Arabi, M. H., , H., Mirzapour, A., Ardestani, M. S. ee, & Saffari, M. (2017). Preparation of nanoliposomes containing Rosmarinus offi cinalis L essential oil; A comparative study. Bioscience Biotechnology Research Communications, 10(1), 103–108. https://doi.org/10.21786/bbrc/10.1/15

Arya, M. A., Manoj Kumar, M. K., Sabitha, M., Menon, K. N., & Nair, S. C. (2019). Nanotechnology approaches for enhanced CNS delivery in treating Alzheimer’s disease. Journal of Drug Delivery Science and Technology, 51, 297–309. https://doi.org/10.1016/j.jddst.2019.03.022

Ashraf, J. M., Ansari, M. A., Fatma, S., Abdullah, S. M. S., Iqbal, J., Madkhali, A., Hamali, A. H., Ahmad, S., Jerah, A., Echeverria, V., Barreto, G. E., & Ashraf, G. M. (2018). Inhibiting Effect of Zinc Oxide Nanoparticles on Advanced Glycation Products and Oxidative Modifications: A Potential Tool to Counteract Oxidative Stress in Neurodegenerative Diseases. Molecular Neurobiology, 55(9), 7438–7452. https://doi.org/10.1007/s12035-018-0935-x

Balducci, C., Mancini, S., Minniti, S., La Vitola, P., Zotti, M., Sancini, G., Mauri, M., Cagnotto, A., Colombo, L., Fiordaliso, F., Grigoli, E., Salmona, M., Snellman, A., Haaparanta-Solin, M., Forloni, G., Masserini, M., & Re, F. (2014). Multifunctional Liposomes Reduce Brain -Amyloid Burden and Ameliorate Memory Impairment in Alzheimer’s Disease Mouse Models. Journal of Neuroscience, 34(42), 14022–14031. https://doi.org/10.1523/JNEUROSCI.0284-14.2014

Baranowska-Wójcik, E., & Szwajgier, D. (2020). Alzheimer’s disease: Review of current nanotechnological therapeutic strategies. Expert Review of Neurotherapeutics, 20(3), 271–279. https://doi.org/10.1080/14737175.2020.1719069

Barbosa, F. O., Assis, G. B., Araújo, L. V., Pinheiro, M. J. da C., Lemos, G. D., Maia, C. S., Assis, T. de O., & Lemos-Jordão, A. J. J. M. (2020). Doença de Alzheimer e o uso de memantina: Uma revisão da literatura. Brazilian Journal of Health Review, 3(2), 2415–2425. https://doi.org/10.34119/bjhrv3n2-091

Barret, O., Alagille, D., Sanabria, S., Comley, R. A., Weimer, R. M., Borroni, E., Mintun, M., Seneca, N., Papin, C., Morley, T., Marek, K., Seibyl, J. P., Tamagnan, G. D., & Jennings, D. (2017). Kinetic Modeling of the Tau PET Tracer 18 F-AV-1451 in Human Healthy Volunteers and Alzheimer Disease Subjects. Journal of Nuclear Medicine, 58(7), 1124–1131. https://doi.org/10.2967/jnumed.116.182881

Catalán, J., & Norppa, H. (2017). Safety Aspects of Bio-Based Nanomaterials. Bioengineering, 4(4), 94. https://doi.org/10.3390/bioengineering4040094

Dunn, B., Stein, P., & Cavazzoni, P. (2021). Approval of Aducanumab for Alzheimer Disease—The FDA’s Perspective. JAMA Internal Medicine, 181(10), 1276. https://doi.org/10.1001/jamainternmed.2021.4607

Fulop, T., Witkowski, J. M., Bourgade, K., Khalil, A., Zerif, E., Larbi, A., Hirokawa, K., Pawelec, G., Bocti, C., Lacombe, G., Dupuis, G., & Frost, E. H. (2018). Can an Infection Hypothesis Explain the Beta Amyloid Hypothesis of Alzheimer’s Disease? Frontiers in Aging Neuroscience, 10, 224. https://doi.org/10.3389/fnagi.2018.00224

Gao, C., Chu, X., Gong, W., Zheng, J., Xie, X., Wang, Y., Yang, M., Li, Z., Gao, C., & Yang, Y. (2020). Neuron tau-targeting biomimetic nanoparticles for curcumin delivery to delay progression of Alzheimer’s disease. Journal of Nanobiotechnology, 18(1), 71. https://doi.org/10.1186/s12951-020-00626-1

Gao, N., Sun, H., Dong, K., Ren, J., & Qu, X. (2015). Gold-Nanoparticle-Based Multifunctional Amyloid-β Inhibitor against Alzheimer’s Disease. Chemistry - A European Journal, 21(2), 829–835. https://doi.org/10.1002/chem.201404562

Geng, J., Li, M., Ren, J., Wang, E., & Qu, X. (2011). Polyoxometalates as Inhibitors of the Aggregation of Amyloid β Peptides Associated with Alzheimer’s Disease. Angewandte Chemie International Edition, 50(18), 4184–4188. https://doi.org/10.1002/anie.201007067

Hampel, H., Mesulam, M.-M., Cuello, A. C., Farlow, M. R., Giacobini, E., Grossberg, G. T., Khachaturian, A. S., Vergallo, A., Cavedo, E., Snyder, P. J., & Khachaturian, Z. S. (2018a). The cholinergic system in the pathophysiology and treatment of Alzheimer’s disease. Brain, 141(7), 1917–1933. https://doi.org/10.1093/brain/awy132

Hampel, H., Mesulam, M.-M., Cuello, A. C., Khachaturian, A. S., Vergallo, A., Farlow, M. R., Snyder, P. J., Giacobini, E., & Khachaturian, Z. S. (2018b). Revisiting the Cholinergic Hypothesis in Alzheimer's Disease: Emerging Evidence from Translational and Clinical Research. The Journal Of Prevention of Alzheimer’s Disease, 1–14. https://doi.org/10.14283/jpad.2018.43

Herrán, E., Pérez-González, R., Igartua, M., Pedraz, J. L., Carro, E., & Hernández, R. M. (2013). VEGF-releasing biodegradable nanospheres administered by craniotomy: A novel therapeutic approach in the APP/Ps1 mouse model of Alzheimer’s disease. Journal of Controlled Release, 170(1), 111–119. https://doi.org/10.1016/j.jconrel.2013.04.028

Hock, F. J., & Gralinski, M. R. (Eds.). (2020). Drug Discovery and Evaluation: Methods in Clinical Pharmacology. Springer International Publishing. https://doi.org/10.1007/978-3-319-68864-0

Huang, G., Xie, J., Shuai, S., Wei, S., Chen, Y., Guan, Z., Zheng, Q., Yue, P., & Wang, C. (2021). Nose-to-brain delivery of drug nanocrystals by using Ca2+ responsive deacetylated gellan gum based in situ-nanogel. International Journal of Pharmaceutics, 594, 120182. https://doi.org/10.1016/j.ijpharm.2020.120182

Jia, Y.-P., Ma, B.-Y., Wei, X.-W., & Qian, Z.-Y. (2017). The in vitro and in vivo toxicity of gold nanoparticles. Chinese Chemical Letters, 28(4), 691–702. https://doi.org/10.1016/j.cclet.2017.01.021

Karthivashan, G., Ganesan, P., Park, S.-Y., Kim, J.-S., & Choi, D.-K. (2018). Therapeutic strategies and nano-drug delivery applications in management of ageing Alzheimer’s disease. Drug Delivery, 25(1), 307–320. https://doi.org/10.1080/10717544.2018.1428243

Kumar, R., Umar, A., Kumar, G., & Nalwa, H. S. (2017). Antimicrobial properties of ZnO nanomaterials: A review. Ceramics International, 43(5), 3940–3961. https://doi.org/10.1016/j.ceramint.2016.12.062

Lemoine, L., Gillberg, P.-G., Svedberg, M., Stepanov, V., Jia, Z., Huang, J., Nag, S., Tian, H., Ghetti, B., Okamura, N., Higuchi, M., Halldin, C., & Nordberg, A. (2017). Comparative binding properties of the tau PET tracers THK5117, THK5351, PBB3, and T807 in postmortem Alzheimer brains. Alzheimer’s Research & Therapy, 9(1), 96. https://doi.org/10.1186/s13195-017-0325-z

León-Silva, S., Fernández-Luqueño, F., & López-Valdez, F. (2018). Engineered Nanoparticles: Are They an Inestimable Achievement or a Health and Environmental Concern? Em F. López-Valdez & F. Fernández-Luqueño (Eds.), Agricultural Nanobiotechnology (pp. 183–212). Springer International Publishing. https://doi.org/10.1007/978-3-319-96719-6_10

Li, A., Tyson, J., Patel, S., Patel, M., Katakam, S., Mao, X., & He, W. (2021). Emerging Nanotechnology for Treatment of Alzheimer’s and Parkinson’s Disease. Frontiers in Bioengineering and Biotechnology, 9, 672594. https://doi.org/10.3389/fbioe.2021.672594

Li, Y., Cheng, Q., Jiang, Q., Huang, Y., Liu, H., Zhao, Y., Cao, W., Ma, G., Dai, F., Liang, X., Liang, Z., & Zhang, X. (2014). Enhanced endosomal/lysosomal escape by distearoyl phosphoethanolamine-polycarboxybetaine lipid for systemic delivery of siRNA. Journal of Controlled Release, 176, 104–114. https://doi.org/10.1016/j.jconrel.2013.12.007

Li, Z., Cong, H., Yan, Z., Liu, A., & Yu, B. (2018). The Potential Human Health and Environmental Issues of Nanomaterials. Em Handbook of Nanomaterials for Industrial Applications (pp. 1049–1054). Elsevier. https://doi.org/10.1016/B978-0-12-813351-4.00060-2

Ling, T. S., Chandrasegaran, S., Xuan, L. Z., Suan, T. L., Elaine, E., Nathan, D. V., Chai, Y. H., Gunasekaran, B., & Salvamani, S. (2021). The Potential Benefits of Nanotechnology in Treating Alzheimer’s Disease. BioMed Research International, 2021, 1–9. https://doi.org/10.1155/2021/5550938

Ma, R., Zhang, Y., Hong, X., Zhang, J., Wang, J.-Z., & Liu, G. (2017). Role of microtubule-associated protein tau phosphorylation in Alzheimer’s disease. Journal of Huazhong University of Science and Technology [Medical Sciences], 37(3), 307–312. https://doi.org/10.1007/s11596-017-1732-x

Marinho, K. S. N., Antonio, E. A., Silva, C. V. N. S., Silva, K. T. D., Teixeira, V. W., Aguiar Junior, F. C. A. D., Santos, K. R. P. D., Silva, N. H. D., & Santos, N. P. S. (2017). Hepatic toxicity caused by PLGA-microspheres containing usnic acid from the lichen C ladonia substellata (AHTI) during pregnancy in Wistar rats. Anais Da Academia Brasileira de Ciências, 89(2), 1073–1084. https://doi.org/10.1590/0001-3765201720160650

Menghani, Y. R., Bhattad, D. M., Chandak, K. K., Taksande, J. R., & Umekar, M. J. (2021). A Review: Pharmacological and herbal remedies in The Management of Neurodegenerative disorder (Alzheimer’s). International Journal of Pharmacognosy and Life Science, 2(1), 18–27. https://doi.org/10.33545/27072827.2021.v2.i1a.23

Menon, J. U., Kona, S., Wadajkar, A. S., Desai, F., Vadla, A., & Nguyen, K. T. (2012). Effects of surfactants on the properties of PLGA nanoparticles. Journal of Biomedical Materials Research Part A, 100A(8), 1998–2005. https://doi.org/10.1002/jbm.a.34040

Nikolova, M., Slavchov, R., & Nikolova, G. (2020). Nanotechnology in Medicine. Em F. J. Hock & M. R. Gralinski (Eds.), Drug Discovery and Evaluation: Methods in Clinical Pharmacology (pp. 533–546). Springer International Publishing. https://doi.org/10.1007/978-3-319-68864-0_45

Nishu, S. D., Park, S., Ji, Y., Han, I., Key, J., & Lee, T. K. (2020). The effect of engineered PLGA nanoparticles on nitrifying bacteria in the soil environment. Journal of Industrial and Engineering Chemistry, 84, 297–304. https://doi.org/10.1016/j.jiec.2020.01.011

Organization for Economic Cooperation and Development. (2017). Health at a Glance 2017: OECD Indicators. OECD. https://doi.org/10.1787/health_glance-2017-en

Ono, M., Sahara, N., Kumata, K., Ji, B., Ni, R., Koga, S., Dickson, D. W., Trojanowski, J. Q., Lee, V. M.-Y., Yoshida, M., Hozumi, I., Yoshiyama, Y., van Swieten, J. C., Nordberg, A., Suhara, T., Zhang, M.-R., & Higuchi, M. (2017). Distinct binding of PET ligands PBB3 and AV-1451 to tau fibril strains in neurodegenerative tauopathies. Brain, 140(3), 768-780. https://doi.org/10.1093/brain/aww339

Pramanik, D., Ghosh, C., & Dey, S. G. (2011). Heme–Cu Bound Aβ Peptides: Spectroscopic Characterization, Reactivity, and Relevance to Alzheimer’s Disease. Journal of the American Chemical Society, 133(39), 15545–15552. https://doi.org/10.1021/ja204628b

Sajid, M., & Płotka-Wasylka, J. (2020). Nanoparticles: Synthesis, characteristics, and applications in analytical and other sciences. Microchemical Journal, 154, 104623. https://doi.org/10.1016/j.microc.2020.104623

Sharma, N., Tramutola, A., Lanzillotta, C., Arena, A., Blarzino, C., Cassano, T., Butterfield, D. A., Di Domenico, F., Perluigi, M., & Barone, E. (2019). Loss of biliverdin reductase-A favors Tau hyper-phosphorylation in Alzheimer’s disease. Neurobiology of Disease, 125, 176–189. https://doi.org/10.1016/j.nbd.2019.02.003

Sousa, B. M. (2017). Abordagem Terapêutica na Doença de Alzheimer (Dissertação de Mestrado, Faculdade de Ciências e Tecnologia da Universidade do Algarve). http://hdl.handle.net/10400.1/10408

Taylor, M., Moore, S., Mourtas, S., Niarakis, A., Re, F., Zona, C., Ferla, B. L., Nicotra, F., Masserini, M., Antimisiaris, S. G., Gregori, M., & Allsop, D. (2011). Effect of curcumin-associated and lipid ligand-functionalized nanoliposomes on aggregation of the Alzheimer’s Aβ peptide. Nanomedicine: Nanotechnology, Biology and Medicine, 7(5), 541–550. https://doi.org/10.1016/j.nano.2011.06.015

Vaz, M., & Silvestre, S. (2020). Alzheimer’s disease: Recent treatment strategies. European Journal of Pharmacology, 887, 173554. https://doi.org/10.1016/j.ejphar.2020.173554

Walsh, S., Merrick, R., Milne, R., & Brayne, C. (2021). Aducanumab for Alzheimer’s disease? BMJ, 374, n1682. https://doi.org/10.1136/bmj.n1682

Yang, M., Jin, L., Wu, Z., Xie, Y., Zhang, P., Wang, Q., Yan, S., Chen, B., Liang, H., Naman, C. B., Zhang, J., He, S., Yan, X., Zhao, L., & Cui, W. (2021). PLGA-PEG Nanoparticles Facilitate In Vivo Anti-Alzheimer’s Effects of Fucoxanthin, a Marine Carotenoid Derived from Edible Brown Algae. Journal of Agricultural and Food Chemistry, 69(34), 9764–9777. https://doi.org/10.1021/acs.jafc.1c00569

Yiannopoulou, K. G., & Papageorgiou, S. G. (2020). Current and future treatments in Alzheimer disease: An update. Journal of Central Nervous System Disease, 12, 1-12. https://doi.org/10.1177/1179573520907397

Zeng, H., Qi, Y., Zhang, Z., Liu, C., Peng, W., & Zhang, Y. (2021). Nanomaterials toward the treatment of Alzheimer’s disease: Recent advances and future trends. Chinese Chemical Letters, 32(6), 1857–1868. https://doi.org/10.1016/j.cclet.2021.01.014

Zhao, Y., Cai, J., Liu, Z., Li, Y., Zheng, C., Zheng, Y., Chen, Q., Chen, H., Ma, F., An, Y., Xiao, L., Jiang, C., Shi, L., Kang, C., & Liu, Y. (2019). Nanocomposites inhibit the formation, mitigate the neurotoxicity, and facilitate the removal of β-Amyloid Aggregates in Alzheimer’s disease mice. Nano Letters, 19(2), 674–683. https://doi.org/10.1021/acs.nanolett.8b03644

Zhang, L., Zhao, P., Yue, C., Jin, Z., Liu, Q., Du, X., & He, Q. (2019). Sustained release of bioactive hydrogen by Pd hydride nanoparticles overcomes Alzheimer's disease. Biomaterials, 197, 393-404. https://doi.org/10.1016/j.biomaterials.2019.01.037

Published

2022-07-29

How to Cite

Cruz Lopes, L., Lopes, A., Escudeiro, M., Duarte, C., Ferreira, R., Graça, F., Silva, I., & Esteves, B. (2022). Nanoparticles for the treatment of the alzheimer’s disease: review article . Millenium - Journal of Education, Technologies, and Health, 2(10e), 77–92. https://doi.org/10.29352/mill0210e.26245

Issue

Section

Engineering, Technology, Management and Tourism