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Current Drug Metabolism


ISSN (Print): 1389-2002
ISSN (Online): 1875-5453

Review Article

Recent Patents, Regulatory Issues, and Toxicity of Nanoparticles in Neuronal Disorders

Author(s): Abdul Muheem, Mohammed A. Jahangir, Chandra P. Jaiswal, Mohammed Jafar, Mohammad Z. Ahmad, Javed Ahmad and Musarrat H. Warsi*

Volume 22, Issue 4, 2021

Published on: 10 December, 2020

Page: [263 - 279] Pages: 17

DOI: 10.2174/1389200221999201210213036

Price: $65


Background: Form last few decades, nanoparticles have witnessed breakthroughs in the treatment of neurological disorders due to their unique physiochemical properties, which make them an effective drug delivery system. However, there is not much information available on the toxicity of nanoparticles in neuronal disorders. The toxic effect of nanoparticles on brain disorders and their regulatory issues are the primary concerns of the healthcare industry.

Methods: A strategical literature search was performed on various bibliographic databases such as Scopus, PubMed, SciFinder, Google Scholar, Medline, Google Patent, Derwent Innovation, and Orbit Intelligence for retrieval of peer-reviewed articles and patents on regulatory issues and toxicity of nanoparticles in neuronal disorders for last decade. The relevant hits of articles and patents were analyzed, and citation search for the relevant documents was carried out.

Results: The literature documents have been summarized regarding the existing regulatory issues and toxicity of nanoparticles on neuronal disorders with a focus on the detailed mechanism of the developmental toxicity of nanoparticles. The focus of this report is to emphasize the negative effects of nanoparticle on neuronal disorders, which may partially contribute to the management of toxicity of nanoparticles.

Conclusion: Although nanoparticles have unique physical and chemical properties that explain the broad range of application for the central nervous system, they can also manifest neurotoxic effects due to cell necrosis, generation of free radicals, immune responses and neuroinflammation. Thus, this review highlights risk assessment, safety regulations and regulatory guidelines of nanoparticles, which may reduce adverse reactions in humans and animals.

Keywords: Toxicity, neuronal disorder, brain diseases, nanoparticles, regulatory, patent.

Graphical Abstract
Vissers, C.; Ming, G.L.; Song, H. Nanoparticle technology and stem cell therapy team up against neurodegenerative disorders. Adv. Drug Res., 2019, 148, 239-251.
Ramanathan, S.; Archunan, G.; Sivakumar, M.; Selvan, S.T.; Fred, A.L.; Kumar, S.; Gulyás, B.; Padmanabhan, P. Theranostic applications of nanoparticles in neurodegenerative disorders. Int. J. Nanomed., 2018, 13, 5561-5576.
Jacobs, M.; Hart, E.P.; Roos, R.A. Driving with a neurodegenerative disorder: an overview of the current literature. J. Neuro., 2017, 264(8), 1678-96.
Camins, A.; Sureda, F.X.; Junyent, F.; Verdaguer, E.; Folch, J.; Beas-Zarate, C.; Pallas, M. An overview of investigational antiapoptotic drugs with potential application for the treatment of neurodegenerative disorders. Exp. Opin. Invest. Drugs, 2010, 19(5), 587-604.
Rai, M.; Yadav, A.; Ingle, A.P.; Reshetilov, A.; Blanco-Prieto, M.J.; Feitosa, C.M. Neurodegenerative diseases: the real problem and nanobiotechnological solutions. In: Nanobiotech in neurodegenerative diseases; Springer, 2019; pp. 1-17.
Matej, R.; Tesar, A.; Rusina, R. Alzheimer's disease and other neurodegenerative dementias in comorbidity: a clinical and neuropathological overview. Clin. Biochem., 2019, 73, 26-31.
Ahmad, M.Z.; Ahmad, J.; Amin, S.; Rahman, M.; Anwar, M.; Mallick, N.; Ahmad, F.J.; Rahman, Z.; Kamal, M.A.; Akhter, S. Role of nanomedicines in delivery of anti-acetylcholinesterase compounds to the brain in Alzheimer’s disease. CNS Neurol. Disord. Drug Targets, 2014, 13(8), 1315-1324.
Reynolds, J.L.; Mahato, R.I. Nanomedicines for the Treatment of CNS Diseases. J. Neuroimmune Pharmacol., 2017, 12(1), 1-5.
Hernando, S.; Herran, E.; Pedraz, J.L.; Igartua, M.; Hernandez, R.M. Nanotechnology Based Approaches for Neurodegenerative Disorders: Diagnosis and Treatment. In: Drug and Gene Delivery to the Central Nervous System for Neuroprotection; Springer, 2017; pp. 57-87.
Pehlivan, S.B. Nanotechnology-based drug delivery systems for targeting, imaging and diagnosis of neurodegenerative diseases. Pharm Res., 2013, 30(10), 2499-511.
Gulati, M.; Chopra, D.S.; Singh, S.K.; Saluja, V.; Pathak, P.; Bansal, P. Patents on brain permeable nanoparticles. Recent Pat. CNS Drug Discov., 2013, 8(3), 220-234.
Spuch, C.; Saida, O.; Navarro, C. Advances in the treatment of neurodegenerative disorders employing nanoparticles. Recent Pat. Drug Deliv. Formul., 2012, 6(1), 2-18.
Abdulkarim, M.F.; Heard, C.; Alany, G.R. An overview of recent patents on nanoparticles for drug delivery across the blood brain barrier. Recent Pat. Nanomed., 2012, 2(1), 45-51.
Srikanth, M.; Kessler, J.A. Nanotechnology—novel therapeutics for CNS disorders. Nature Rev Neurology., 2012, 8(6), 307-18.
Ahmad, J.; Akhter, S.; Rizwanullah, M.; Khan, M.A.; Pigeon, L.; Addo, R.T.; Greig, N.H.; Midoux, P.; Pichon, C.; Kamal, M.A. Addo, Greig R.T.N, Midoux, P.; Pichon, C.; Amjad, M.K. Nanotechnology based theranostic approaches in Alzheimer’s disease management: current status and future perspective. Curr. Alzheimer Res., 2017, 14(11), 1164-1181.
Md, S.; Bhattmisra, S.K.; Zeeshan, F.; Shahzad, N.; Mujtaba, M.A.; Meka, V.S.; Radhakrishnan, A.; Kesharwani, P.; Baboota, S.; Ali, J. Nano-carrier enabled drug delivery systems for nose to brain targeting for the treatment of neurodegenerative disorders. J. Drug Deliv. Sci. Technol., 2018, 43, 295-310.
Ahmad, M.Z.; Abdel-Wahab, B.A.; Alam, A.; Zafar, S.; Ahmad, J.; Ahmad, F.J.; Midoux, P.; Pichon, C.; Akhter, S. Toxicity of inorganic nanoparticles used in targeted drug delivery and other biomedical application: an updated account on concern of biomedical nanotoxicology. J. Nanosci. Nanotechnol., 2016, 16(8), 7873-7897.
Tzeyung, A.S.; Md, S.; Bhattamisra, S.K.; Madheswaran, T.; Alhakamy, N.A.; Aldawsari, H.M.; Radhakrishnan, A.K. Fabrication, optimization, and evaluation of rotigotine-loaded chitosan nanoparticles for nose-to-brain delivery. Pharmaceutics, 2019, 11(1), 26.
Nunes, A.; Al-Jamal, K.T.; Kostarelos, K. Therapeutics, imaging and toxicity of nanomaterials in the central nervous system. J. Controlled Rel., 2012, 161(2), 290-306.
Li, J.; Martin, F.L. Current Perspective on Nanomaterial-Induced Adverse Effects: Neurotoxicity as a Case Example. InNeurotoxicity of nanomaterials and nanomedicine. Academic Press; Academic Press, 2017, pp. 75-98.
Mushtaq, G.; Khan, J.A.; Joseph, E.; Kamal, M.A. Nanoparticles, neurotoxicity and neurodegenerative diseases. Curr. Drug Metab., 2015, 16(8), 676-684.
Abbott, N.J.; Patabendige, A.A.K.; Dolman, D.E.M.; Yusof, S.R.; Begley, D.J. Structure and function of the blood-brain barrier. Neurobiol. Dis., 2010, 37(1), 13-25.
Boyer-Di Ponio, J.; El-Ayoubi, F.; Glacial, F.; Ganeshamoorthy, K.; Driancourt, C.; Godet, M.; Perrière, N.; Guillevic, O.; Couraud, P.O.; Uzan, G. Instruction of circulating endothelial progenitors in vitro towards specialized blood-brain barrier and arterial phenotypes. PLoS One, 2014, 9(1), e84179.
Huber, J.D.; Witt, K.A.; Hom, S.; Egleton, R.D.; Mark, K.S.; Davis, T.P. Inflammatory pain alters blood-brain barrier permeability and tight junctional protein expression. Am. J. Physiol. Heart Circ. Physiol., 2001, 280(3), H1241-H1248.
Wahl, M.; Unterberg, A.; Baethmann, A.; Schilling, L. Mediators of blood-brain barrier dysfunction and formation of vasogenic brain edema. J. Cereb. Blood Flow Metab., 1988, 8(5), 621-634.
Petty, M.A.; Lo, E.H. Junctional complexes of the blood-brain barrier: permeability changes in neuroinflammation. Prog. Neurobiol., 2002, 68(5), 311-323.
Saeedi, M.; Eslamifar, M.; Khezri, K.; Dizaj, S.M. Applications of nanotechnology in drug delivery to the central nervous system. Biomed. Pharmacother., 2019, 111, 666-675.
Gao, H. Progress and perspectives on targeting nanoparticles for brain drug delivery. Acta Pharm. Sin. B, 2016, 6(4), 268-286.
Jain, K.K. Nanobiotechnology-based strategies for crossing the blood-brain barrier. Nanomedicine (Lond.), 2012, 7(8), 1225-1233.
Barar, J.; Rafi, M.A.; Pourseif, M.M.; Omidi, Y. Blood-brain barrier transport machineries and targeted therapy of brain diseases. Bioimpacts, 2016, 6(4), 225-248.
Tamai, I.; Tsuji, A. Transporter-mediated permeation of drugs across the blood-brain barrier. J. Pharm. Sci., 2000, 89(11), 1371-1388.
Kanwar, J.R.; Sun, X.; Punj, V.; Sriramoju, B.; Mohan, R.R.; Zhou, S.F.; Chauhan, A.; Kanwar, R.K. Nanoparticles in the treatment and diagnosis of neurological disorders: untamed dragon with fire power to heal. Nanomedicine (Lond.), 2012, 8(4), 399-414.
Witt, K.A.; Huber, J.D.; Egleton, R.D.; Davis, T.P. Insulin enhancement of opioid peptide transport across the blood-brain barrier and assessment of analgesic effect. J. Pharmacol. Exp. Ther., 2000, 295(3), 972-978.
Fiori, A.; Cardelli, P.; Negri, L.; Savi, M.R.; Strom, R.; Erspamer, V. Deltorphin transport across the blood-brain barrier. Proc. Natl. Acad. Sci. USA, 1997, 94(17), 9469-9474.
Wilson, B.; Samanta, M.K.; Santhi, K.; Kumar, K.P.S.; Paramakrishnan, N.; Suresh, B. Poly(n-butylcyanoacrylate) nanoparticles coated with polysorbate 80 for the targeted delivery of rivastigmine into the brain to treat Alzheimer’s disease. Brain Res., 2008, 1200, 159-168.
Roney, C.; Kulkarni, P.; Arora, V.; Antich, P.; Bonte, F.; Wu, A.; Mallikarjuana, N.N.; Manohar, S.; Liang, H.F.; Kulkarni, A.R.; Sung, H.W.; Sairam, M.; Aminabhavi, T.M. Targeted nanoparticles for drug delivery through the blood-brain barrier for Alzheimer’s disease. J. Control. Release, 2005, 108(2-3), 193-214.
Aderibigbe, B.A.; Naki, T. Chitosan-Based Nanocarriers for Nose to Brain Delivery. Appl. Sci. (Basel), 2019, 9, 1-27.
Kumagai, A.K.; Eisenberg, J.B.; Pardridge, W.M. Absorptive-mediated endocytosis of cationized albumin and a beta-endorphin-cationized albumin chimeric peptide by isolated brain capillaries. Model system of blood-brain barrier transport. J. Biol. Chem., 1987, 262(31), 15214-15219.
dos Santos, W.L.; Rahman, J.; Klein, N.; Male, D.K. Distribution and analysis of surface charge on brain endothelium in vitro and in situ. Acta Neuropathol., 1995, 90(3), 305-311.
Juillerat-Jeanneret, L. The targeted delivery of cancer drugs across the blood-brain barrier: chemical modifications of drugs or drug-nanoparticles? Drug Discov. Today, 2008, 13(23-24), 1099-1106.
Seferos, D.S.; Giljohann, D.A.; Rosi, N.L.; Mirkin, C.A. Locked nucleic acid-nanoparticle conjugates. ChemBioChem, 2007, 8(11), 1230-1232.
Khongkow, M.; Yata, T.; Boonrungsiman, S.; Rungsardthong, U.R.; Graham, D.; Namdee, K. Surface modification of gold nanoparticles with neuron-targeted exosome for enhanced blood–brain barrier penetration, 2019, 9, 1-9.
Lu, C.T.; Zhao, Y.Z.; Wong, H.L.; Cai, J.; Peng, L.; Tian, X.Q. Current approaches to enhance CNS delivery of drugs across the brain barriers. Int. J. Nanomedicine, 2014, 9(10), 2241-2257.
Athira, J.S.; Prajitha, N.; Mohanan, P. Interaction of nanoparticles with central nervous system and its consequences. Am J Res Med Sci., 2018, 4(1), 12-32.
Poduslo, J.F.; Curran, G.L.; Wengenack, T.M.; Malester, B.; Duff, K. Permeability of proteins at the blood-brain barrier in the normal adult mouse and double transgenic mouse model of Alzheimer’s disease. Neurobiol. Dis., 2001, 8(4), 555-567.
Laron, Z. Insulin and the brain. Arch. Physiol. Biochem., 2009, 115(2), 112-116.
Saraiva, C.; Praça, C.; Ferreira, R.; Santos, T.; Ferreira, L.; Bernardino, L. Nanoparticle-mediated brain drug delivery: overcoming blood-brain barrier to treat neurodegenerative diseases. J. Control. Release, 2016, 235, 34-47.
Sahoo, S.K.; Labhasetwar, V. Enhanced antiproliferative activity of transferrin-conjugated paclitaxel-loaded nanoparticles is mediated via sustained intracellular drug retention. Mol. Pharm., 2005, 2(5), 373-383.
De Jong, W.H.; Borm, P.J. Drug delivery and nanoparticles:applications and hazards. Int. J. Nanomedicine, 2008, 3(2), 133-149.
Voinea, M.; Simionescu, M. Designing of ‘intelligent’ liposomes for efficient delivery of drugs. J. Cell. Mol. Med., 2002, 6(4), 465-474.
Mora, M.; Sagristá, M.L.; Trombetta, D.; Bonina, F.P.; De Pasquale, A.; Saija, A. Design and characterization of liposomes containing long-chain N-acylPEs for brain delivery: penetration of liposomes incorporating GM1 into the rat brain. Pharm. Res., 2002, 19(10), 1430-1438.
Costantino, L.; Tosi, G.; Ruozi, B.; Bondioli, L.; Vandelli, M.A.; Forni, F. Colloidal systems for CNS drug delivery. Prog Brain Res., Elsevier Science B. V: Amsterdam 2009, 180, 35-69.
Sercombe, L.; Veerati, T.; Moheimani, F.; Wu, S.Y.; Sood, A.K.; Hua, S. Hua, S1. Advances and challenges of liposome assisted drug delivery. Front. Pharmacol., 2015, 6, 286.
Olson, F.; Hunt, C.A.; Szoka, F.C.; Vail, W.J.; Papahadjopoulos, D. Preparation of liposomes of defined size distribution by extrusion through polycarbonate membranes. Biochimica et Biophysica Acta Biomembran, 1979, 557, 9-23.
Yu, B.; Lee, R.J.; Lee, L.J. Microfluidic methods for production of liposomes. Methods Enzymol., 2009, 465, 129-141.
Xie, R.; Dong, L.; Du, Y.; Zhu, Y.; Hua, R.; Zhang, C.; Chen, X. In vivo metabolic labeling of sialoglycans in the mouse brain by using a liposome-assisted bioorthogonal reporter strategy. Proc. Natl. Acad. Sci. USA, 2016, 113(19), 5173-5178.
Zhang, Y.; Zhai, M.; Chen, Z.; Han, X.; Yu, F.; Li, Z.; Xie, X.; Han, C.; Yu, L.; Yang, Y.; Mei, X. Dual-modified liposome codelivery of doxorubicin and vincristine improve targeting and therapeutic efficacy of glioma. Drug Deliv., 2017, 24(1), 1045-1055.
Gao, H.; Qian, J.; Cao, S.; Yang, Z.; Pang, Z.; Pan, S.; Fan, L.; Xi, Z.; Jiang, X.; Zhang, Q. Precise glioma targeting of and penetration by aptamer and peptide dual-functioned nanoparticles. Biomaterials, 2012, 33(20), 5115-5123.
Xiyang, S.; Lijun, M. Nanometer drug delivery system targeted for brain tumors and tumor stem cells thereof and preparation and application of nanometer drug delivery system. CN Patent 110179753, August 30, 2019.
Shengrong, G.; Dejian, Z.; Li, L. Polycurcumin based amphiphilic block copolymer and application thereof. CN Patent 105646861, July 03, 2018.
Sung, S.H.; Ki, M.S.; Yeoseon, K. A pharmaceutical composition comprising liposome containing phycocyanin or phycoerythrin as an active ingredient for brain disease. KR Patent 1898528, September 13, 2018.
Hui, K. Liposome composition for relieving symptoms of parkinson's disease and alzheimer's disease. US Patent 20190151242, May 23, 2019.
Zhengzhi, W.; Lin, W. Invisible brain-targeted triptolide nano-liposome and preparation method. CN Patent 107899022, April 13, 2018.
Zhou, J.; Han, L.; Piepmeier, J.M. Compositions for enhancing delivery of agents across the blood brain barrier and methods of use thereof. US Patent 20180126014, May 10, 2018.
Changyou, Z.; Zui, Z. Amyloid β short peptide mediated brain targeted delivery system, preparation method therefor and use thereof. PCT Patent WO2019/237884, December 19, 2019.
Weiyue, L.; Tongcheng, D.; Cao, X. Adenosine monophosphate AMP complex and application thereof in preparation of tumor targeting nano-drug delivery system. CN Patent 110051854, July 26, 2019.
Panagiota, P.; Gabriela, A.A.; Frederick, C.; Jeroen, B.; Alexander, K. Delivery vectors. PCT Patent WO2019/083365, May 02, 2019.
Gustafson, H.H.; Holt-Casper, D.; Grainger, D.W.; Ghandehari, H. Nanoparticle Uptake: The Phagocyte Problem. Nano Today, 2015, 10(4), 487-510.
Hu, Y.L.; Qi, W.; Han, F.; Shao, J.Z.; Gao, J.Q. Toxicity evaluation of biodegradable chitosan nanoparticles using a zebrafish embryo model. Int. J. Nanomedicine, 2011, 6, 3351-3359.
Battaglia, L.; Gallarate, M. Lipid nanoparticles: state of the art, new preparation methods and challenges in drug delivery. Expert Opin. Drug Deliv., 2012, 9(5), 497-508.
Lasa-Saracibar, B.; Estella-Hermoso de Mendoza, A.; Guada, M.; Dios-Vieitez, C.; Blanco-Prieto, M.J. Lipid nanoparticles for cancer therapy: state of the art and future prospects. Expert Opin. Drug Deliv., 2012, 9(10), 1245-1261.
Müller, R.H.; Mäder, K.; Gohla, S. Solid lipid nanoparticles (SLN) for controlled drug delivery - a review of the state of the art. Eur. J. Pharm. Biopharm., 2000, 50(1), 161-177.
Müller, R.H.; Maassen, S.; Weyhers, H.; Mehnert, W. Phagocytic uptake and cytotoxicity of solid lipid nanoparticles (SLN) sterically stabilized with poloxamine 908 and poloxamer 407. J. Drug Target., 1996, 4(3), 161-170.
Maxwell, C.J.; Hogan, D.B.; Ebly, E.M. Calcium-channel blockers and cognitive function in elderly people: results from the Canadian Study of Health and Aging. CMAJ, 1999, 161(5), 501-506.
Bhattacharya, S. Preparation and evaluation of solid lipid nano particles for cancer treatment. IN Patent 201721019625, July 12, 2019.
Kaili, H.; Liping, W.; Luting, W.; Junfeng, D.; Jianfang, F.; Mei, L. Brain-targeting nanometer medication system modified by brain guiding drug and preparation method of brain-targeting nanometer medication system. CN Patent 107029247, August 11, 2017.
Wei, Y.; Xichong, Y.; Yingzheng, Z. Medicine preparation for treating brain diseases. CN Patent 105381469, March 09, 2016.
Rongrong, Z.; Lingjing, J. Application of compound to preparation of drug for treating Parkinson's disease. CN Patent 106138053, May 09, 2019.
Alexander, W.; Jeremy, R. Methods and compositions for parenteral administration of cannabidiol in the treatment of convulsive disorders. PCT Patent WO2019/094625, May 16, 2019.
Sally, F.A.; Gregory, C.M. Bioavailable curcuminoid formulations for treating Alzheimer's disease and other age-related disorders. US Patent 9192644, September 2007.
Weber, S.; Zimmer, A.; Pardeike, J. Solid Lipid Nanoparticles (SLN) and Nanostructured Lipid Carriers (NLC) for pulmonary application: a review of the state of the art. Eur. J. Pharm. Biopharm., 2014, 86(1), 7-22.
Iqbal, M.A.; Md, S.; Sahni, J.K.; Baboota, S.; Dang, S.; Ali, J. Nanostructured lipid carriers system: recent advances in drug delivery. J. Drug Target., 2012, 20(10), 813-830.
Jaiswal, P.; Gidwani, B.; Vyas, A. Nanostructured lipid carriers and their current application in targeted drug delivery. Artif. Cells Nanomed. Biotechnol., 2016, 44(1), 27-40.
Kasongo, K.W.; Müller, R.H.; Walker, R.B. The use of hot and cold high pressure homogenization to enhance the loading capacity and encapsulation efficiency of nanostructured lipid carriers for the hydrophilic antiretroviral drug, didanosine for potential administration to paediatric patients. Pharm. Dev. Technol., 2012, 17(3), 353-362.
Beloqui, A.; Solinís, M.A.; Rodríguez-Gascón, A.; Almeida, A.J.; Préat, V. Nanostructured lipid carriers: Promising drug delivery systems for future clinics. Nanomedicine (Lond.), 2016, 12(1), 143-161.
Lim, W.M.; Rajinikanth, P.S.; Mallikarjun, C.; Kang, Y.B. Formulation and delivery of itraconazole to the brain using a nanolipid carrier system. Int. J. Nanomedicine, 2014, 9, 2117-2126.
Joseph, E.; Saha, R.N. Advances in brain targeted drug delivery: nanoparticulate systems. J. Pharm. Sci. Technol., 2013, 3(1), 1-8.
Georgieva, J.V.; Hoekstra, D.; Zuhorn, I.S. Smuggling drugs into the brain: an overview of ligands targeting transcytosis for drug delivery across the blood-brain barrier. Pharmaceutics, 2014, 6(4), 557-583.
Nasiri, M.; Azadi, A.; Zanjani, M.R.S.; Hamidi, M. Indinavir-loaded nanostructured lipid carriers to brain drug delivery: optimization, characterization and neuropharmacokinetic evaluation. Curr. Drug Deliv., 2019, 16(4), 341-354.
Emami, J.; Yousefian, H.; Sadeghi, H. Targeted nanostructured lipid carrier for brain delivery of artemisinin: design, preparation, characterization, optimization and cell toxicity. J. Pharm. Pharm. Sci., 2018, 21(1s), 225s-241s.
Srinivas, M.; Suresh, M.R.; Shreya, A.B.; Sushil, Y.R. Nanostructured lipid carriers containing atypical antipsychotic drug for oral administration. IN Patent 201841005172, August 16, 2019.
Shailendra, B.V.; Vijaysing, P.C. Novel nanocarrier composition for brain targeting. IN Patent 0667/MUM/2015, April 28, 2017.
Woo, K.S. Composition for increasing expression Of PGC-1alpha. US Patent 20190,030,053, January 31, 2019.
Mishra, V.; Kesharwani, P.; Kesherwani, P. Dendrimer technologies for brain tumor. Drug Discov. Today, 2016, 21(5), 766-778.
Kannan, R.; Sujatha, K.; Elizabeth, N.; Blue, M.E.; Michael, V.J.; William, B.; Fan, Z.; Ann, W.M.; Barbara, S. Dendrimer compositions and use in treatment of neurological and cns disorders. US Patent 20170232120, August 17, 2017.
Yanhong, S.; Qi, C.; Su, Y. Targeting glioblastoma stem cells through the tlx-tet3 axis. US Patent 20190032055, January 31, 2019.
Harada-Shiba, M.; Yamauchi, K.; Harada, A.; Takamisawa, I.; Shimokado, K.; Kataoka, K. Polyion complex micelles as vectors in gene therapy pharmacokinetics 2002. Gene Ther., 2002, 9, 407-414.
Torchilin, V.P. Micellar nanocarriers: pharmaceutical perspectives. Pharm. Res., 2007, 24(1), 1-16.
Yajie, W.; Heng, L.; Mingzhen, Y.; Zhiqing, P.; Ning, W.; Yiran, W. Preparation method of amphipathic block nano-micelle carrying lapatinib and brain-targeted nano-micelle. CN Patent 106619512, May 10, 2017.
Das, B.; Vedachalam, S.; Luo, D.; Antonio, T.; Reith, M.E.; Dutta, A.K. Development of a highly potent D2/D3 agonist and a partial agonistfrom structure-activity relationship study of N(6)-(2-(4-(1H-Indol-5-yl)piperazin-1-yl)ethyl)-N(6)-propyl-4,5,6, 7-tetrahydroben zo [d]thiazole-2,6-diamine Analogues: implication in the treatment of Parkinson’s disease. J. Med. Chem., 2015, 58(23), 9179-9195.
Chan, C.S.; Gertler, T.S.; Surmeier, D.J. A molecular basis for the increased vulnerability of substantia nigra dopamine neurons in aging and Parkinson’s disease. Mov. Disord., 2010, 25, 63-70.
Xu, Q.; Kanthasamy, A.G.; Reddy, M.B. Neuroprotective effect of the natural iron chelator, phytic acid in a cell culture model of Parkinson’s disease. Toxicology, 2008, 245(1-2), 101-108.
Wang, N.; Jin, X.; Guo, D.; Tong, G.; Zhu, X. Iron chelation nanoparticles with delayed saturation as an effective therapy for Parkinson disease. Biomacromolecules, 2017, 18(2), 461-474.
Shah, S.A.; Yoon, G.H.; Chung, S.S.; Abid, M.N.; Kim, T.H.; Lee, H.Y.; Kim, M.O. Novel osmotin inhibits SREBP2 via the AdipoR1/AMPK/SIRT1 pathway to improve Alzheimer’s disease neuropathological deficits. Mol. Psychiatry, 2017, 22(3), 407-416.
Zaijun, L.; Kun, S.; Beihua, K.; Shu, Y.; Cunzhong, Y. Doxorubicin hydrochloride magnetic nanoparticles and preparation method thereof. CN Patent 106265514, July 05, 2019.
Daishun, L.; Li, F. Nano composite material, preparation method and application. CN Patent 109771644, May 21, 2019.
Yun, L.D.; Jae, L.S.; Shik, K.H. Lactoferrin-conjugated nanoparticle complex and use thereof. US Patent 20170281797, October 05, 2017.
Valdiglesias, V.; Kiliç, G.; Costa, C.; Fernández-Bertólez, N.; Pásaro, E.; Teixeira, J.P.; Laffon, B. Effects of iron oxide nanoparticles: cytotoxicity, genotoxicity, developmental toxicity, and neurotoxicity. Environ. Mol. Mutagen., 2015, 56(2), 125-148.
Muller, A.P.; Ferreira, G.K.; Pires, A.J.; de Bem Silveira, G.; de Souza, D.L.; Brandolfi, J.A.; de Souza, C.T.; Paula, M.M.S.; Silveira, P.C.L. Gold nanoparticles prevent cognitive deficits, oxidative stress and inflammation in a rat model of sporadic dementia of Alzheimer’s type. Mater. Sci. Eng. C, 2017, 77, 476-483.
Kim, M.J.; Rehman, S.U.; Amin, F.U.; Kim, M.O. Enhanced neuroprotection of anthocyanin-loaded PEG-gold nanoparticles against Aβ1-42-induced neuroinflammation and neurodegeneration via the NF-KB/JNK/GSK3β signaling pathway. Nanomedicine (Lond.), 2017, 13(8), 2533-2544.
Xiong, N.; Zhao, Y.; Dong, X.; Zheng, J.; Sun, Y. Design of a molecular hybrid of dual peptide inhibitors coupled on AuNPs for enhanced inhibition of Amyloid beta-protein aggregation and cytotoxicity. Small, 2017, 13(13), 1-14.
Pitt, J.; Wilcox, K.C.; Tortelli, V.; Diniz, L.P.; Oliveira, M.S.; Dobbins, C.; Yu, X.W.; Nandamuri, S.; Gomes, F.C.A.; DiNunno, N.; Viola, K.L.; De Felice, F.G.; Ferreira, S.T.; Klein, W.L. Neuroprotective astrocyte-derived insulin/insulin-like growth factor 1 stimulates endocytic processing and extracellular release of neuron-bound Aβ oligomers. Mol. Biol. Cell, 2017, 28(20), 2623-2636.
Ying-chen, Y.; Chia-nan, C.; Li-ling, C. Use of nano metal in promoting neurite outgrowth and treatment and/or prevention of neurological disorders. US Patent 9655923, May 23, 2017.
Liu, X.; Sui, B.; Sun, J. Blood-brain barrier dysfunction induced by silica NPs in vitro and in vivo: involvement of oxidative stress and Rho-kinase/JNK signaling pathways. Biomaterials, 2017, 121, 64-82.
Xie, H.; Wu, J. Silica nanoparticles induce alpha-synuclein induction and aggregation in PC12-cells. Chem. Biol. Interact., 2016, 258, 197-204.
Bayat Mokhtari, R.; Homayouni, T.S.; Baluch, N.; Morgatskaya, E.; Kumar, S.; Das, B.; Yeger, H. Combination therapy in combating cancer. Oncotarget, 2017, 8(23), 38022-38043.
Zhou, J.; Fa, H.; Yin, W.; Zhang, J.; Hou, C.; Huo, D.; Zhang, D.; Zhang, H. Synthesis of superparamagnetic iron oxide nanoparticles coated with a DDNP-carboxyl derivative for in vitro magnetic resonance imaging of Alzheimer’s disease. Mater. Sci. Eng. C, 2014, 37, 348-355.
Cheng, K.K.; Chan, P.S.; Fan, S.; Kwan, S.M.; Yeung, K.L.; Wáng, Y.X.; Chow, A.H.; Wu, E.X.; Baum, L. Curcumin-conjugated magnetic nanoparticles for detecting amyloid plaques in Alzheimer’s disease mice using magnetic resonance imaging (MRI). Biomaterials, 2015, 44, 155-172.
Yip, L.W.; Yin, L.H. Fatty acid conjugated nanoparticles and uses thereof. US Patent 20190029970, January 31, 2019.
Cong, L.; Xihui, G.; Huihui, Y. Cross-blood-brain-barrier targeting multimodal nano-medicine used in brain tumor diagnosis. CN Patent 103083689, August 03, 2016.
Young-suk, P.; Jae, K.S. Nano micelle comprising drug quantum dot and targeting agent and use thereof. KR Patent 1977532, May 10, 2019.
Vinayak, D.P. Magnetic nanostructures as theranostic agents. US Patent 9801952, October 31, 2017.
Wadghiri, Y.Z.; Li, J.; Wang, J.; Hoang, D.M.; Sun, Y.; Xu, H.; Tsui, W.; Li, Y.; Boutajangout, A.; Wang, A.; de Leon, M.; Wisniewski, T. Detection of amyloid plaques targeted by bifunctional USPIO in Alzheimer’s disease transgenic mice using magnetic resonance microimaging. PLoS One, 2013, 8(2), e57097.
Shilo, M.; Motiei, M.; Hana, P.; Popovtzer, R. Transport of nanoparticles through the blood-brain barrier for imaging and therapeutic applications. Nanoscale, 2014, 6(4), 2146-2152.
Yu, Y.Y.; Zhang, L.; Sun, X.Y.; Li, C.L.; Qiu, Y.; Sun, H.P.; Tang, D.Q.; Liu, Y.W.; Yin, X.X. A sensitive colorimetric strategy for monitoring cerebral β-amyloid peptides in AD based on dual-functionalized gold nanoplasmonic particles. Chem. Commun. (Camb.), 2015, 51(42), 8880-8883.
Cong, L.; Xihui, G.; Qi, Y. Bimodal nanoprobes for image-guided brain tumor resection. CN Patent 107837403, March 27, 2018.
Xing, Y.; Xia, Z.; Rao, J. Semiconductor quantum dots for biosensing and in vivo imaging. IEEE Trans. Nanobioscience, 2009, 8(1), 4-12.
Huo, Q. A perspective on bioconjugated nanoparticles and quantum dots. Colloids Surf. B Biointerfaces, 2007, 59(1), 1-10.
Yibiao, L.; Guangli, H.; Pengfei, N.; Mengdan, H.; Weipeng, Q.; Pingping, Z.; Shouren, Z.; Baocheng, Y. Electrochemical immunosensor for detecting alzheimer's disease markers and preparation method and application thereof. CN Patent 110006976, July 12, 2019.
Wagner, V.; Dullaart, A.; Bock, A.K.; Zweck, A. The emerging nanomedicine landscape. Nat. Biotechnol., 2006, 24(10), 1211-1217.
Sainz, V.; Conniot, J.; Matos, A.I.; Peres, C.; Zupancic, E.; Moura, L.; Silva, L.C.; Florindo, H.F.; Gaspar, R.S. Regulatory aspects on nanomedicines. Biochem. Biophys. Res. Commun., 2015, 468(3), 504-510.
Duncan, R.; Gaspar, R. Nanomedicine(s) under the microscope. Mol. Pharm., 2011, 8(6), 2101-2141.
Tinkle, S.; McNeil, S.E.; Mühlebach, S.; Bawa, R.; Borchard, G.; Barenholz, Y.C.; Tamarkin, L.; Desai, N. Nanomedicines: addressing the scientific and regulatory gap. Ann. N. Y. Acad. Sci., 2014, 1313, 35-56.
Aggarwal, P.; Hall, J.B.; McLeland, C.B.; Dobrovolskaia, M.A.; McNeil, S.E. Nanoparticle interaction with plasma proteins as it relates to particle biodistribution, biocompatibility and therapeutic efficacy. Adv. Drug Deliv. Rev., 2009, 61(6), 428-437.
Dobrovolskaia, M.A.; McNeil, S.E. Understanding the correlation between in vitro and in vivo immunotoxicity tests for nanomedicines. J. Control. Release, 2013, 172(2), 456-466.
Wolfram, J.; Zhu, M.; Yang, Y.; Shen, J.; Gentile, E.; Paolino, D.; Fresta, M.; Nie, G.; Chen, C.; Shen, H.; Ferrari, M.; Zhao, Y. Safety of nanoparticles in medicine. Curr. Drug Targets, 2015, 16(14), 1671-1681.
Coty, J.B.; Vauthier, C. Characterization of nanomedicines: a reflection on a field under construction needed for clinical translation success. J. Control. Release, 2018, 275, 254-268.
Gaspar, R. Therapeutic products: regulating drugs and medical devices. In: International handbook on Regulating Nanotechnologies; Hodge, G.A.; Bowman, D.M.; Maynard, A.D., Eds.; Edward Elgar Publishing limited: Northampton, MA, USA, 2010; pp. 291-320.
Win-Shwe, T-T.; Fujimaki, H. Nanoparticles and neurotoxicity. Int. J. Mol. Sci., 2011, 12(9), 6267-6280.
Teleanu, D.M.; Chircov, C.; Grumezescu, A.M.; Volceanov, A.; Teleanu, R.I. Impact of nanoparticles on brain health: an up to date overview. J. Clin. Med., 2018, 7(12), 490.
von Bohlen Und Halbach, O. Immunohistological markers for staging neurogenesis in adult hippocampus. Cell Tissue Res., 2007, 329(3), 409-420.
Feng, X.; Chen, A.; Zhang, Y.; Wang, J.; Shao, L.; Wei, L. Central nervous system toxicity of metallic nanoparticles. Int. J. Nanomedicine, 2015, 10(1), 4321-4340.
Teleanu, D.M.; Chircov, C.; Grumezescu, A.M.; Teleanu, R.I. Neurotoxicity of nanomaterials: an up-to-date overview. Nanomaterials (Basel), 2019, 9(1), 96.
Shvedova, A.; Pietroiusti, A.; Kagan, V. Nanotoxicology ten years later: lights and shadows. Toxicol. Appl. Pharmacol., 2016, 299, 1-2.
Caudle, W.M. Occupational metal exposure and parkinsonism. In: Neurotoxicity of Metals; Aschner, M.; Costa, L.G., Eds.; Springer: New York, NY, USA, 2017; pp. 143-158.
Lovisolo, D.; Dionisi, M.; Ruffinatti, F.A.; Distasi, C. Nanoparticles and potential neurotoxicity: focus on molecular mechanisms. AIMS Mol. Sci., 2018, 2(5), 1-3.
Muheem, A.; Shakeel, F.; Warsi, M.H.; Jain, G.K.; Ahmad, F.J. A combinatorial statistical design approach to optimize the nanostructured cubosomal carrier system for oral delivery of ubidecarenone for management of doxorubicin-induced cardiotoxicity: in vitro-in vivo investigations. J. Pharm. Sci., 2017, 106(10), 3050-3065.
Bencsik, A.; Lestaevel, P.; Canu, I.G. Nano-and neurotoxicology: an emerging discipline. Prog. Neurobiol., 2018, 160, 45-63.
Teleanu, D.M.; Chircov, C.; Grumezescu, A.M.; Teleanu, R.I. Neuronanomedicine: an up-to-date overview. Pharmaceutics, 2019, 11(3), 1-23.
Yuan, Z-Y.; Hu, Y-L.; Gao, J-Q. Brain localization and neurotoxicity evaluation of polysorbate 80-modified chitosan nanoparticles in rats. PLoS One, 2015, 10(8), e0134722.
Huo, T.; Barth, R.F.; Yang, W.; Nakkula, R.J.; Koynova, R.; Tenchov, B.; Chaudhury, A.R.; Agius, L.; Boulikas, T.; Elleaume, H.; Lee, R.J. Preparation, biodistribution and neurotoxicity of liposomal cisplatin following convection enhanced delivery in normal and F98 glioma bearing rats. PLoS One, 2012, 7(11), e48752.
You, R.; Ho, Y-S.; Hung, C.H-L.; Liu, Y.; Huang, C-X.; Chan, H-N.; Ho, S-L.; Lui, S-Y.; Li, H-W.; Chang, R.C-C. Silica nanoparticles induce neurodegeneration-like changes in behavior, neuropathology, and affect synapse through MAPK activation. Part. Fibre Toxicol., 2018, 15(1), 28.

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