BRAIN-TARGETED NANO-DRUG DELIVERY FOR THE TREATMENT OF PARKINSON'S DISEASE

Yıl 2024, Cilt: 1 Sayı: 2, 77 - 92, 29.06.2024

Reşat Altay Yergök Serap Derman Jahid Alakbarli Ahmad Safvan Eskhıta

https://doi.org/10.5281/zenodo.12510571

Öz

Parkinson’s Disease affects 2% to 3% of overall individuals aged 65 years or older worldwide and is considered to be the second most common age-related neurodegenerative disease. Neuropathologic features of Parkinson’s Disease attributes to a loss of pigmented dopaminergic neurons in the substantia nigra and the formation of Lewy Bodies, as a result of intracellular accumulation of α-synuclein proteins. To our current day, only a few therapeutic approaches are considered promising, one of which is the Nanoscale approach. It gives an advantage over conventional approaches by offering solutions to complications that occur in the current treatment methods used for Parkinson’s Disease, namely by encapsulating and protecting the drug from extracellular degradations, allowing for a more sustained, efficient, and targeted drug release profile, thus reducing the risk of adverse effects of the drug used. In this study, we review, discuss, and briefly explain the nanoscale approaches, alternative administration routes, and studies conducted in vivo and in vitro for an efficient treatment and an alternative approach to Parkinson’s Disease.

Anahtar Kelimeler

Blood–Brain Barrier, Nano-drug Delivery, Nanoparticles, Parkinson's Disease

Kaynakça

• Abedi-Gaballu, F., Dehghan, G., Ghaffari, M., Yekta, R., Abbaspour-Ravasjani, S., Baradaran, B., Ezzati Nazhad Dolatabadi, J., & Hamblin, M. R. (2018). PAMAM dendrimers as efficient drug and gene delivery nanosystems for cancer therapy. In Applied Materials Today (Vol. 12, pp. 177–190). Elsevier Ltd. https://doi.org/10.1016/j.apmt.2018.05.002
• Agrawal, M., Ajazuddin, Tripathi, D. K., Saraf, S., Saraf, S., Antimisiaris, S. G., Mourtas, S., Hammarlund-Udenaes, M., & Alexander, A. (2017). Recent advancements in liposomes targeting strategies to cross blood-brain barrier (BBB) for the treatment of Alzheimer’s disease. In Journal of Controlled Release (Vol. 260, pp. 61–77). Elsevier B.V. https://doi.org/10.1016/j.jconrel.2017.05.019
• Alexander, K. (2018). Biomedical Applications of Nano-Sized Polymeric Micelles and Polyion Complexes. Journal of Siberian Federal University. Biology, 11(2), 110–118. https://doi.org/10.17516/1997-1389-0053
• Arango, D., Bittar, A., Esmeral, N. P., Ocasión, C., Muñoz-Camargo, C., Cruz, J. C., Reyes, L. H., & Bloch, N. I. (2021). Understanding the Potential of Genome Editing in Parkinson’s Disease. International Journal of Molecular Sciences 2021, Vol. 22, Page 9241, 22(17), 9241. https://doi.org/10.3390/IJMS22179241
• Azeem, A., Talegaonkar, S., Negi, L. M., Ahmad, F. J., Khar, R. K., & Iqbal, Z. (2012). Oil based nanocarrier system for transdermal delivery of ropinirole: A mechanistic, pharmacokinetic and biochemical investigation. International Journal of Pharmaceutics, 422(1–2), 436–444. https://doi.org/10.1016/j.ijpharm.2011.10.039
• Balestrino, R., & Schapira, A. H. V. (2020). Parkinson disease. European Journal of Neurology, 27(1), 27–42. https://doi.org/10.1111/ENE.14108
• Banerjee, D., Das, P. K., & Mukherjee, J. (2023). Nervous System. Textbook of Veterinary Physiology, 265–293. https://doi.org/10.1007/978-981-19-9410-4_11
• Batrakova, E. v., & Kim, M. S. (2015). Using exosomes, naturally-equipped nanocarriers, for drug delivery. Journal of Controlled Release, 219, 396–405. https://doi.org/10.1016/j.jconrel.2015.07.030
• Bolger, G. T. (2018). Routes of Drug Administration ☆. In Reference Module in Biomedical Sciences. Elsevier. https://doi.org/10.1016/B978-0-12-801238-3.11099-2
• Braak, H., del Tredici, K., Rüb, U., de Vos, R. A. I., Jansen Steur, E. N. H., & Braak, E. (2003). Staging of brain pathology related to sporadic Parkinson’s disease. Neurobiology of Aging, 24(2), 197–211. https://doi.org/10.1016/S0197-4580(02)00065-9
• Castro, K. C. de, Costa, J. M., & Campos, M. G. N. (2022). Drug-loaded polymeric nanoparticles: a review. International Journal of Polymeric Materials and Polymeric Biomaterials, 71(1), 1–13. https://doi.org/10.1080/00914037.2020.1798436
• Chen, M., Quan, G., Sun, Y., Yang, D., Pan, X., & Wu, C. (2020). Nanoparticles-encapsulated polymeric microneedles for transdermal drug delivery. Journal of Controlled Release, 325, 163–175. https://doi.org/10.1016/j.jconrel.2020.06.039
• Chillag-Talmor, O., Giladi, N., Linn, S., Gurevich, T., El-Ad, B., Silverman, B., Friedman, N., & Peretz, C. (2011). Use of a refined drug tracer algorithm to estimate prevalence and incidence of Parkinson’s disease in a large israeli population. Journal of Parkinson’s Disease, 1(1), 35–47. https://doi.org/10.3233/JPD-2011-11024
• da Silva Córneo, E., de Bem Silveira, G., Scussel, R., Correa, M. E. A. B., da Silva Abel, J., Luiz, G. P., Feuser, P. E., Silveira, P. C. L., & Machado-de-Ávila, R. A. (2020). Effects of gold nanoparticles administration through behavioral and oxidative parameters in animal model of Parkinson’s disease. Colloids and Surfaces B: Biointerfaces, 196, 111302. https://doi.org/10.1016/j.colsurfb.2020.111302
• Date, A. A., Hanes, J., & Ensign, L. M. (2016). Nanoparticles for oral delivery: Design, evaluation and state-of-the-art. Journal of Controlled Release, 240, 504–526. https://doi.org/10.1016/j.jconrel.2016.06.016 de Bem Silveira, G., Muller, A. P., Machado-De-Ávila, R. A., & Silveira, P. C. L. (2021). Advance in the use of gold nanoparticles in the treatment of neurodegenerative diseases: New perspectives. In Neural Regeneration Research (Vol. 16, Issue 12, pp. 2425–2426). Wolters Kluwer Medknow Publications. https://doi.org/10.4103/1673-5374.313040
• Ding, S., Khan, A. I., Cai, X., Song, Y., Lyu, Z., Du, D., Dutta, P., & Lin, Y. (2020). Overcoming blood-brain barrier transport: Advances in nanoparticle-based drug delivery strategies. Materials Today (Kidlington, England), 37, 112. https://doi.org/10.1016/J.MATTOD.2020.02.001
• Duan, Y., Dhar, A., Patel, C., Khimani, M., … S. N.-R., & 2020, undefined. (n.d.). A brief review on solid lipid nanoparticles: Part and parcel of contemporary drug delivery systems. Pubs.Rsc.Org. Retrieved July 13, 2022, from https://pubs.rsc.org/en/content/articlehtml/2020/ra/d0ra03491f
• Dudhipala, N., & Gorre, T. (2020). Neuroprotective Effect of Ropinirole Lipid Nanoparticles Enriched Hydrogel for Parkinson’s Disease: İn vitro, Ex Vivo, Pharmacokinetic and Pharmacodynamic Evaluation. Pharmaceutics, 12(5), 448. https://doi.org/10.3390/pharmaceutics12050448
• Dykman, L. A., & Khlebtsov, N. G. (2011). Gold Nanoparticles in Biology and Medicine: Recent Advances and Prospects. Acta Naturae, 3(2), 34–55. https://doi.org/10.32607/20758251-2011-3-2-34-56
• Enriquez-Traba, J., Yarur-Castillo, H. E., Flores, R. J., Weil, T., Roy, S., Usdin, T. B., LaGamma, C. T., Arenivar, M., Wang, H., Tsai, V. S., Moritz, A. E., Sibley, D. R., Moratalla, R., Freyberg, Z. Z., & Tejeda, H. A. (2023). Dissociable control of motivation and reinforcement by distinct ventral striatal dopamine receptors. BioRxiv, 2023.06.27.546539. https://doi.org/10.1101/2023.06.27.546539
• Esposito, E., Fantin, M., Marti, M., Drechsler, M., Paccamiccio, L., Mariani, P., Sivieri, E., Lain, F., Menegatti, E., Morari, M., & Cortesi, R. (2008). Solid lipid nanoparticles as delivery systems for bromocriptine. Pharmaceutical
• Research, 25(7), 1521–1530. https://doi.org/10.1007/s11095-007-9514-y Fang, J. Y., Hung, C. F., Chi, C. H., & Chen, C. C. (2009). Transdermal permeation of selegiline from hydrogel-membrane drug delivery systems. International Journal of Pharmaceutics, 380(1–2), 33–39. https://doi.org/10.1016/j.ijpharm.2009.06.025
• Ferrer-Lorente, R., Lozano-Cruz, T., Fernández-Carasa, I., Miłowska, K., de La Mata, F. J., Bryszewska, M., Consiglio, A., Ortega, P., Gómez, R., & Raya, A. (2021). Cationic Carbosilane Dendrimers Prevent Abnormal α-Synuclein Accumulation in Parkinson’s Disease Patient-Specific Dopamine Neurons. Biomacromolecules, 22(11), 4582–4591. https://doi.org/10.1021/acs.biomac.1c00884
• Fields, C. R., Bengoa-Vergniory, N., & Wade-Martins, R. (2019). Targeting Alpha-Synuclein as a Therapy for Parkinson’s Disease. Frontiers in Molecular Neuroscience, 12, 496177. https://doi.org/10.3389/FNMOL.2019.00299/BIBTEX
• Gaba, B., Khan, T., Haider, M. F., Alam, T., Baboota, S., Parvez, S., & Ali, J. (2019). Vitamin E Loaded Naringenin Nanoemulsion via Intranasal Delivery for the Management of Oxidative Stress in a 6-OHDA Parkinson’s Disease Model. BioMed Research International, 2019. https://doi.org/10.1155/2019/2382563
• Gambaryan, P. Y., Kondrasheva, I. G., Severin, E. S., Guseva, A. A., & Kamensky, A. A. (2014). Increasing the Effciency of Parkinson’s Disease Treatment Using a poly(lactic-co-glycolic acid) (PLGA) Based L-DOPA Delivery System. Experimental Neurobiology, 23(3), 246–252. https://doi.org/10.5607/en.2014.23.3.246
• Gartziandia, O., Herran, E., Pedraz, J. L., Carro, E., Igartua, M., & Hernandez, R. M. (2015). Chitosan coated nanostructured lipid carriers for brain delivery of proteins by intranasal administration. Colloids and Surfaces B: Biointerfaces, 134, 304–313. https://doi.org/10.1016/j.colsurfb.2015.06.054
• Gonzalez-Carter, D. A., Leo, B. F., Ruenraroengsak, P., Chen, S., Goode, A. E., Theodorou, I. G., Chung, K. F., Carzaniga, R., Shaffer, M. S. P., Dexter, D. T., Ryan, M. P., & Porter, A. E. (2017). Silver nanoparticles reduce brain inflammation and related neurotoxicity through induction of H 2 S-synthesizing enzymes. Scientific Reports, 7. https://doi.org/10.1038/srep42871
• Guimarães, D., Cavaco-Paulo, A., & Nogueira, E. (2021). Design of liposomes as drug delivery system for therapeutic applications. In International Journal of Pharmaceutics (Vol. 601, p. 120571). Elsevier B.V. https://doi.org/10.1016/j.ijpharm.2021.120571
• Haider, M., Abdin, S. M., Kamal, L., & Orive, G. (2020). Nanostructured Lipid Carriers for Delivery of Chemotherapeutics: A Review. Pharmaceutics, 12(3), 288. https://doi.org/10.3390/pharmaceutics12030288
• Haney, M. J., Klyachko, N. L., Zhao, Y., Gupta, R., Plotnikova, E. G., He, Z., Patel, T., Piroyan, A., Sokolsky, M., Kabanov, A. v., & Batrakova, E. v. (2015). Exosomes as drug delivery vehicles for Parkinson’s disease therapy. Journal of Controlled Release, 207, 18–30. https://doi.org/10.1016/j.jconrel.2015.03.033
• Herholz, K. (2008). Acetylcholine esterase activity in mild cognitive impairment and Alzheimer’s disease. In European Journal of Nuclear Medicine and Molecular Imaging (Vol. 35, Issue SUPPL. 1, pp. 25–29). Springer. https://doi.org/10.1007/s00259-007-0699-4
• Hernando, S., Herran, E., Figueiro-Silva, J., Pedraz, J. L., Igartua, M., Carro, E., & Hernandez, R. M. (2018). Intranasal administration of TAT-conjugated lipid nanocarriers loading GDNF for Parkinson’s disease. Molecular Neurobiology, 55(1), 145–155. https://doi.org/10.1007/s12035-017-0728-7
• Hu, K., Shi, Y., Jiang, W., Han, J., Huang, S., & Jiang, X. (2011). Lactoferrin conjugated PEG-PLGA nanoparticles for brain delivery: Preparation, characterization and efficacy in Parkinsons disease. International Journal of Pharmaceutics, 415(1–2), 273–283. https://doi.org/10.1016/j.ijpharm.2011.05.062
• Huang, R., Ke, W., Liu, Y., Wu, D., Feng, L., Jiang, C., & Pei, Y. (2010). Gene therapy using lactoferrin-modified nanoparticles in a rotenone-induced chronic Parkinson model. Journal of the Neurological Sciences, 290(1–2), 123–130. https://doi.org/10.1016/j.jns.2009.09.032 Iacono, D., Geraci-Erck, M., Rabin, M. L., Adler, C. H., Serrano, G., Beach, T. G., & Kurlan, R. (2015). Parkinson disease and incidental Lewy body disease: Just a question of time? Neurology, 85(19), 1670–1679. https://doi.org/10.1212/WNL.0000000000002102
• Kabanov, A., & Batrakova, E. (2005). New Technologies for Drug Delivery Across the Blood Brain Barrier. Current Pharmaceutical Design, 10(12), 1355–1363. https://doi.org/10.2174/1381612043384826
• Kabanov, A. V., & Gendelman, H. E. (2007). Nanomedicine in the diagnosis and therapy of neurodegenerative disorders. In Progress in Polymer Science (Oxford) (Vol. 32, Issues 8–9, pp. 1054–1082). Pergamon. https://doi.org/10.1016/j.progpolymsci.2007.05.014
• Kane, R. S., & Stroock, A. D. (2007). Nanobiotechnology: Protein-Nanomaterial Interactions. Biotechnology Progress, 23(2), 316–319. https://doi.org/10.1021/bp060388n Kikuchi, T., Morizane, A., Doi, D., Magotani, H., Onoe, H., Hayashi, T., Mizuma, H., Takara, S., Takahashi, R., Inoue, H.,
• Morita, S., Yamamoto, M., Okita, K., Nakagawa, M., Parmar, M., & Takahashi, J. (2017). Human iPS cell-derived dopaminergic neurons function in a primate Parkinson’s disease model. Nature, 548(7669), 592–596. https://doi.org/10.1038/NATURE23664
• Kizelsztein, P., Ovadia, H., Garbuzenko, O., Sigal, A., & Barenholz, Y. (2009). Pegylated nanoliposomes remote-loaded with the antioxidant tempamine ameliorate experimental autoimmune encephalomyelitis. Journal of Neuroimmunology, 213(1–2), 20–25. https://doi.org/10.1016/j.jneuroim.2009.05.019
• Leonardi, A., Crascí, L., Panico, A., & Pignatello, R. (2015). Antioxidant activity of idebenone-loaded neutral and cationic solid-lipid nanoparticles. Pharmaceutical Development and Technology, 20(6), 716–723. https://doi.org/10.3109/10837450.2014.915572
• Li, Y., Zhu, Z., Huang, T., Zhou, Y., Wang, X., Yang, L., Chen, Z., Yu, W., & Li, P. (2018). The peripheral immune response after stroke—A double edge sword for blood‐brain barrier integrity. CNS Neuroscience & Therapeutics, 24(12), 1115–1128. https://doi.org/10.1111/cns.13081
• Linhardt, R., Murugesan, S., & Xie, J. (2008). Immobilization of Heparin: Approaches and Applications. Current Topics in Medicinal Chemistry, 8(2), 80–100. https://doi.org/10.2174/156802608783378891
• Łukasiewicz, S., Mikołajczyk, A., Błasiak, E., Fic, E., & Dziedzicka-Wasylewska, M. (2021). Polycaprolactone Nanoparticles as Promising Candidates for Nanocarriers in Novel Nanomedicines. Pharmaceutics, 13(2), 191. https://doi.org/10.3390/pharmaceutics13020191
• Majoral, J. P., Zablocka, M., Ciepluch, K., Milowska, K., Bryszewska, M., Shcharbin, D., Katir, N., el Kadib, A., Caminade, A. M., & Mignani, S. (2021). Hybrid phosphorus-viologen dendrimers as new soft nanoparticles: Design and properties. In Organic Chemistry Frontiers (Vol. 8, Issue 16, pp. 4607–4622). Royal Society of Chemistry. https://doi.org/10.1039/d1qo00511a
• Manatunga, D. C., Godakanda, V. U., Herath, H. M. L. P. B., de Silva, R. M., Yeh, C.-Y., Chen, J.-Y., Akshitha de Silva, A. A., Rajapaksha, S., Nilmini, R., & Nalin de Silva, K. M. (2020). Nanofibrous cosmetic face mask for transdermal delivery of nano gold: synthesis, characterization, release and zebra fish employed toxicity studies. Royal Society Open Science, 7(9), 201266. https://doi.org/10.1098/rsos.201266
• Mao, B. H., Chen, Z. Y., Wang, Y. J., & Yan, S. J. (2018). Silver nanoparticles have lethal and sublethal adverse effects on development and longevity by inducing ROS-mediated stress responses. Scientific Reports, 8(1), 1–16. https://doi.org/10.1038/s41598-018-20728-z
• Marsili, L., Rizzo, G., & Colosimo, C. (2018). Diagnostic criteria for Parkinson’s disease: From James Parkinson to the concept of prodromal disease. In Frontiers in Neurology (Vol. 9, Issue MAR). Frontiers Media S.A. https://doi.org/10.3389/fneur.2018.00156
• McClements, D. J. (2021). Advances in edible nanoemulsions: Digestion, bioavailability, and potential toxicity. In Progress in Lipid Research (Vol. 81, p. 101081). Elsevier Ltd. https://doi.org/10.1016/j.plipres.2020.101081 Md, S., Haque, S., Fazil, M., Kumar, M., Baboota, S., Sahni, J. K., & Ali, J. (2014). Optimised nanoformulation of bromocriptine for direct nose-to-brain delivery: Biodistribution, pharmacokinetic and dopamine estimation by ultra-HPLC/mass spectrometry method. Expert Opinion on Drug Delivery, 11(6), 827–842. https://doi.org/10.1517/17425247.2014.894504
• Mota, J. P. B., & Esteves, I. A. A. C. (2007). Simplified gauge-cell method and its application to the study of capillary phase transition of propane in carbon nanotubes. Adsorption, 13(1), 21–32. https://doi.org/10.1007/s10450-007-9006-8
• Mukhtoraliyeva, S., Tukhtamurodova, Z., & Djuraeva, B. (2024). NERVOUS SYSTEM AND ITS MAIN FUNCTIONS. Евразийский Журнал Медицинских и Естественных Наук, 4(1), 61–67. https://doi.org/10.5281/ZENODO.5884973
• Mustafa, G., Baboota, S., Ahuja, A., & Ali, J. (2012). Formulation Development of Chitosan Coated Intra Nasal Ropinirole Nanoemulsion for Better Management Option of Parkinson: An İn vitro Ex Vivo Evaluation. Current Nanoscience, 8(3), 348–360. https://doi.org/10.2174/157341312800620331
• Nagatsu, T. (2023). Catecholamines and Parkinson’s disease: tyrosine hydroxylase (TH) over tetrahydrobiopterin (BH4) and GTP cyclohydrolase I (GCH1) to cytokines, neuromelanin, and gene therapy: a historical overview. Journal of Neural Transmission (Vienna, Austria : 1996). https://doi.org/10.1007/S00702-023-02673-Y
• Nalls, M. A., Pankratz, N., Lill, C. M., Do, C. B., Hernandez, D. G., Saad, M., Destefano, A. L., Kara, E., Bras, J., Sharma, M., Schulte, C., Keller, M. F., Arepalli, S., Letson, C., Edsall, C., Stefansson, H., Liu, X., Pliner, H., Lee, J. H., … Ansorge, O. (2014). Large-scale meta-analysis of genome-wide association data identifies six new risk loci for Parkinson’s disease. Nature Genetics, 46(9), 989–993. https://doi.org/10.1038/ng.3043
• Nirale, P., Paul, A., & Yadav, K. S. (2020). Nanoemulsions for targeting the neurodegenerative diseases: Alzheimer’s, Parkinson’s and Prion’s. In Life Sciences (Vol. 245, p. 117394). Elsevier Inc. https://doi.org/10.1016/j.lfs.2020.117394
• Onodera, A., Nishiumi, F., Kakiguchi, K., Tanaka, A., Tanabe, N., Honma, A., Yayama, K., Yoshioka, Y., Nakahira, K., Yonemura, S., Yanagihara, I., Tsutsumi, Y., & Kawai, Y. (2015). Short-term changes in intracellular ROS localisation after the silver nanoparticles exposure depending on particle size. Toxicology Reports, 2, 574–579. https://doi.org/10.1016/j.toxrep.2015.03.004
• Pardeshi, C. v, Rajput, P. v, Belgamwar, V. S., Tekade, A. R., & Surana, S. J. (2013a). Drug Delivery Novel surface modified solid lipid nanoparticles as intranasal carriers for ropinirole hydrochloride: application of factorial design approach Novel surface modified solid lipid nanoparticles as intranasal carriers for ropinirole hydrochloride: application of factorial design approach. Drug Deliv, 20(1), 47–56. https://doi.org/10.3109/10717544.2012.752421
• Pardeshi, C. v., Rajput, P. v., Belgamwar, V. S., Tekade, A. R., & Surana, S. J. (2013b). Novel surface modified solid lipid nanoparticles as intranasal carriers for ropinirole hydrochloride: application of factorial design approach. Drug Delivery, 20(1), 47–56. https://doi.org/10.3109/10717544.2012.752421
• Pardridge, W. M. (2005). The blood-brain barrier: Bottleneck in brain drug development. NeuroRx, 2(1), 3–14. https://doi.org/10.1602/neurorx.2.1.3
• Patil, S. M., Sawant, S. S., & Kunda, N. K. (2020). Exosomes as drug delivery systems: A brief overview and progress update. European Journal of Pharmaceutics and Biopharmaceutics, 154, 259–269. https://doi.org/10.1016/j.ejpb.2020.07.026
• Pissuwan, D. (2017). Monitoring and tracking metallic nanobiomaterials in vivo. In Monitoring and Evaluation of Biomaterials and their Performance İn vivo (pp. 135–149). Elsevier Inc. https://doi.org/10.1016/B978-0-08-100603-0.00007-9
• Poewe, W., Seppi, K., Tanner, C. M., Halliday, G. M., Brundin, P., Volkmann, J., Schrag, A. E., & Lang, A. E. (2017). Parkinson disease. Nature Reviews Disease Primers, 3(1), 1–21. https://doi.org/10.1038/nrdp.2017.13
• Przedborski, S., Vila, M., & Jackson-Lewis, V. (2003). Series Introduction: Neurodegeneration: What is it and where are we? Journal of Clinical Investigation, 111(1), 3. https://doi.org/10.1172/JCI17522
• Pulgar, V. M. (2019). Transcytosis to cross the blood brain barrier, new advancements and challenges. Frontiers in Neuroscience, 13(JAN), 1019. https://doi.org/10.3389/fnins.2018.01019
• Rabiei, M., Kashanian, S., Samavati, S. S., Jamasb, S., & McInnes, S. J. P. (2020). Nanomaterial and advanced technologies in transdermal drug delivery. In Journal of Drug Targeting (Vol. 28, Issue 4, pp. 356–367). Taylor and Francis Ltd. https://doi.org/10.1080/1061186X.2019.1693579
• Rekas, A., Lo, V., Gadd, G. E., Cappai, R., & Yun, S. I. (2009). PAMAM Dendrimers as Potential Agents against Fibrillation of α -Synuclein, a Parkinson’s Disease-Related Protein. Macromolecular Bioscience, 9(3), 230–238. https://doi.org/10.1002/mabi.200800242
• Rhea, E. M., & Banks, W. A. (2021). Interactions of Lipids, Lipoproteins, and Apolipoproteins with the Blood-Brain Barrier. In Pharmaceutical Research (Vol. 38, Issue 9, pp. 1469–1475). Springer. https://doi.org/10.1007/s11095-021-03098-6
• Saeedi, M., Eslamifar, M., Khezri, K., & Dizaj, S. M. (2019). Applications of nanotechnology in drug delivery to the central nervous system. In Biomedicine and Pharmacotherapy (Vol. 111, pp. 666–675). Elsevier Masson SAS. https://doi.org/10.1016/j.biopha.2018.12.133
• Sahin, A., Yoyen-Ermis, D., Caban-Toktas, S., Horzum, U., Aktas, Y., Couvreur, P., Esendagli, G., & Capan, Y. (2017). Evaluation of brain-targeted chitosan nanoparticles through blood–brain barrier cerebral microvessel endothelial cells. Journal of Microencapsulation, 34(7), 659–666. https://doi.org/10.1080/02652048.2017.1375039
• Shahnawaz, M., Mukherjee, A., Pritzkow, S., Mendez, N., Rabadia, P., Liu, X., Hu, B., Schmeichel, A., Singer, W., Wu, G., Tsai, A. L., Shirani, H., Nilsson, K. P. R., Low, P. A., & Soto, C. (2020). Discriminating α-synuclein strains in Parkinson’s disease and multiple system atrophy. Nature, 578(7794), 273–277. https://doi.org/10.1038/S41586-020-1984-7
• Sharma, G., Sharma, A. R., Lee, S. S., Bhattacharya, M., Nam, J. S., & Chakraborty, C. (2019). Advances in nanocarriers enabled brain targeted drug delivery across blood brain barrier. In International Journal of Pharmaceutics (Vol. 559, pp. 360–372). Elsevier B.V. https://doi.org/10.1016/j.ijpharm.2019.01.056
• Silva, S., Almeida, A. J., & Vale, N. (2021). Importance of nanoparticles for the delivery of antiparkinsonian drugs. Pharmaceutics, 13(4). https://doi.org/10.3390/pharmaceutics13040508
• Souto, E. B., Baldim, I., Oliveira, W. P., Rao, R., Yadav, N., Gama, F. M., & Mahant, S. (2020). SLN and NLC for topical, dermal, and transdermal drug delivery. In Expert Opinion on Drug Delivery (Vol. 17, Issue 3, pp. 357–377). Taylor and Francis Ltd. https://doi.org/10.1080/17425247.2020.1727883
• Spector, R. (2000). Drug transport in the mammalian central nervous system: Multiple complex systems. A critical analysis and commentary. In Pharmacology (Vol. 60, Issue 2, pp. 58–73). S. Karger AG. https://doi.org/10.1159/000028349
• Stoker, T. B., Torsney, K. M., & Barker, R. A. (2018). Emerging treatment approaches for Parkinson’s disease. Frontiers in Neuroscience, 12(OCT), 419092. https://doi.org/10.3389/FNINS.2018.00693/BIBTEX
• Su, Y., Sun, B., Gao, X., Dong, X., Fu, L., Zhang, Y., Li, Z., Wang, Y., Jiang, H., & Han, B. (2020). Intranasal Delivery of Targeted Nanoparticles Loaded With miR-132 to Brain for the Treatment of Neurodegenerative Diseases. Frontiers in Pharmacology, 11, 1165. https://doi.org/10.3389/fphar.2020.01165
• Sultatos, L. (2007). First-pass effect. In xPharm: The Comprehensive Pharmacology Reference (pp. 1–2). Elsevier Inc. https://doi.org/10.1016/B978-008055232-3.60022-4
• Sun, M., Cheng, R., Xu, X., & Chen, Y. (2006). Studies on adsorption of phenol and substituted phenols on carbon nanotubes. EDITORIAL BOARD OF CHEMICAL ….
• Galatage, S. T., Hebalkar, A. S., Dhobale, S. V., Mali, O. R., Kumbhar, P. S., Nikade, S. V., & Killedar, S. G. (2021). Silver nanoparticles: properties, synthesis, characterization, applications and future trends. Silver micro-nanoparticles—Properties, synthesis, characterization, and applications.
• Teleanu, D., Chircov, C., Grumezescu, A., Volceanov, A., & Teleanu, R. (2018). Blood-Brain Delivery Methods Using Nanotechnology. Pharmaceutics, 10(4), 269. https://doi.org/10.3390/pharmaceutics10040269
• Tsai, M. J., Huang, Y. bin, Wu, P. C., Fu, Y. S., Kao, Y. R., Fang, J. Y., & Tsai, Y. H. (2011). Oral apomorphine delivery from solid lipid nanoparticleswith different monostearate emulsifiers: Pharmacokinetic and behavioral evaluations. Journal of Pharmaceutical Sciences, 100(2), 547–557. https://doi.org/10.1002/jps.22285
• Üner, M. (2015). Characterization and imaging of solid lipid nanoparticles and nanostructured lipid carriers. In Handbook of Nanoparticles (pp. 117–141). Springer International Publishing. https://doi.org/10.1007/978-3-319-15338-4_3
• Vekrellis, K., Xilouri, M., Emmanouilidou, E., Rideout, H. J., & Stefanis, L. (2011). Pathological roles of α-synuclein in neurological disorders. In The Lancet Neurology (Vol. 10, Issue 11, pp. 1015–1025). Elsevier. https://doi.org/10.1016/S1474-4422(11)70213-7
• Venkatas, J., & Singh, M. (2021). Nanomedicine-mediated optimization of immunotherapeutic approaches in cervical cancer. Nanomedicine, 16(15), 1311–1328. https://doi.org/10.2217/nnm-2021-0044
• von Roemeling, C., Jiang, W., Chan, C. K., Weissman, I. L., & Kim, B. Y. S. (2017). Breaking Down the Barriers to Precision Cancer Nanomedicine. In Trends in Biotechnology (Vol. 35, Issue 2, pp. 159–171). Elsevier Ltd. https://doi.org/10.1016/j.tibtech.2016.07.006
• Wang, F., Yang, Z., Liu, M., Tao, Y., Li, Z., Wu, Z., & Gui, S. (2020). Facile nose-to-brain delivery of rotigotine-loaded polymer micelles thermosensitive hydrogels: İn vitro characterization and in vivo behavior study. International Journal of Pharmaceutics, 577, 119046. https://doi.org/10.1016/j.ijpharm.2020.119046
• Wang, Y., Xu, H., Fu, Q., Ma, R., & Xiang, J. (2011). Protective effect of resveratrol derived from Polygonum cuspidatum and its liposomal form on nigral cells in Parkinsonian rats. Journal of the Neurological Sciences, 304(1–2), 29–34. https://doi.org/10.1016/j.jns.2011.02.025
• Xue, J., Liu, T., Liu, Y., Jiang, Y., Seshadri, V. D. D., Mohan, S. K., & Ling, L. (2019). Neuroprotective effect of biosynthesised gold nanoparticles synthesised from root extract of Paeonia moutan against Parkinson disease – İn vitro & İn vivo model. Journal of Photochemistry and Photobiology B: Biology, 200, 111635. https://doi.org/10.1016/j.jphotobiol.2019.111635
• Yang, D., Chen, M., Sun, Y., Jin, Y., Lu, C., Pan, X., Quan, G., & Wu, C. (2021). Microneedle-mediated transdermal drug delivery for treating diverse skin diseases. In Acta Biomaterialia (Vol. 121, pp. 119–133). Acta Materialia Inc. https://doi.org/10.1016/j.actbio.2020.12.004
• Yang, Z., Zhang, Y., Yang, Y., Sun, L., Han, D., Li, H., & Wang, C. (2010). Pharmacological and toxicological target organelles and safe use of single-walled carbon nanotubes as drug carriers in treating Alzheimer disease. Nanomedicine: Nanotechnology, Biology, and Medicine, 6(3), 427–441. https://doi.org/10.1016/j.nano.2009.11.007
• Zhao, M., Brunk, U. T., & Eaton, J. W. (2001). Delayed oxidant-induced cell death involves activation of phospholipase A2. FEBS Letters, 509(3), 399–404. https://doi.org/10.1016/S0014-5793(01)03184-2
• Zhao, Y., Haney, M. J., Gupta, R., Bohnsack, J. P., He, Z., Kabanov, A. v., & Batrakova, E. v. (2014). GDNF-Transfected Macrophages Produce Potent Neuroprotective Effects in Parkinson’s Disease Mouse Model. PLoS ONE, 9(9), e106867. https://doi.org/10.1371/journal.pone.0106867
• Zhao, Y., Xiong, S., Liu, P., Liu, W., Wang, Q., Liu, Y., Tan, H., Chen, X., Shi, X., Wang, Q., & Chen, T. (2020). Polymeric nanoparticles-based brain delivery with improved therapeutic efficacy of ginkgolide b in parkinson’s disease. International Journal of Nanomedicine, 15, 10453–10467. https://doi.org/10.2147/IJN.S272831
• Zhou, Y., Peng, Z., Seven, E. S., & Leblanc, R. M. (2018). Crossing the blood-brain barrier with nanoparticles. Journal of Controlled Release, 270, 290–303. https://doi.org/10.1016/J.JCONREL.2017.12.015
• Zhu, Y., Liu, C., & Pang, Z. (2019). Dendrimer-Based Drug Delivery Systems for Brain Targeting. Biomolecules, 9(12), 790. https://doi.org/10.3390/biom9120790