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Current Drug Delivery

Editor-in-Chief

ISSN (Print): 1567-2018
ISSN (Online): 1875-5704

Research Article

An In vivo Investigation of Ascorbic Acid Tethered Polymeric Nanoparticles for Effectual Brain Transport of Rivastigmine

Author(s): Kavita R. Gajbhiye* and Vandana Soni

Volume 20, Issue 7, 2023

Published on: 26 August, 2022

Page: [961 - 977] Pages: 17

DOI: 10.2174/1567201819666220516093425

Price: $65

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Abstract

Introduction: The goal of this study was to see if ascorbic acid grafted polylactic glycolic acid-b-polyethylene glycol nanoparticles (PLGA-b-PEG NPs) might boost the carrying or transport capacity of rivastigmine(RSM) to the brain via choroid plexus Sodium-dependent vitamin C transporter 2 (SVCT2 transporters). The IR and 1H NMR, were used to characterise the PLGA-b-PEG copolymer.

Methods: Nanoprecipitation method was used to make PLGA-b-PEG NPs. To promote SVCT2- mediated transportation of ascorbic acid (Asc) into the brain, PLGA-b-PEG NPs of acceptable size, polydispersity, and drug loading were bound with ascorbic acid (PLGA-b-PEG-Asc). When compared to PLGA-b-mPEG NPs, the surface functionalization of NPs with ascorbic acid dramatically improved the cellular uptake of NPs in SVCT2 expressing NIH/3T3 cells. Radial Arm Maze Test, and Acetylcholinesterase (AChE) activity in scopolamine-induced amnetic rats were used to assess in vivo pharmacodynamic effectiveness.

Results: In vivo pharmacodynamic tests revealed that drug loaded PLGA-b-PEG-Asc NPs had much greater therapeutic and sustained activity than free drugs, and PLGA-b-mPEG NPs to the brain.

Conclusion: As a consequence, the findings revealed that using ascorbic acid grafted PLGA-b-PEG NPs to deliver bioactives to the brain is a potential strategy.

Keywords: Ascorbic acid, Dementia, PEGylation, Rivastigmine, Targeted Drug Delivery System.

Graphical Abstract

[1]
DeTure, M.A.; Dickson, D.W. The neuropathological diagnosis of Alzheimer’s disease. Mol. Neurodegener., 2019, 14(1), 32.
[http://dx.doi.org/10.1186/s13024-019-0333-5] [PMID: 31375134]
[2]
Karch, C.M.; Goate, A.M. Alzheimer’s disease risk genes and mechanisms of disease pathogenesis. Biol. Psychiatry, 2015, 77(1), 43-51.
[http://dx.doi.org/10.1016/j.biopsych.2014.05.006] [PMID: 24951455]
[3]
Ryan, N.S.; Rossor, M.N.; Fox, N.C. Alzheimer’s disease in the 100 years since Alzheimer’s death. Brain, 2015, 138(Pt 12), 3816-3821.
[http://dx.doi.org/10.1093/brain/awv316] [PMID: 26541346]
[4]
Ashraf, G.M.; Greig, N.H.; Khan, T.A.; Hassan, I.; Tabrez, S.; Shakil, S.; Sheikh, I.A.; Zaidi, S.K.; Akram, M.; Jabir, N.R.; Firoz, C.K.; Naeem, A.; Alhazza, I.M.; Damanhouri, G.A.; Kamal, M.A. Protein misfolding and aggregation in Alzheimer’s disease and type 2 diabetes mellitus. CNS Neurol. Disord. Drug Targets, 2014, 13(7), 1280-1293.
[http://dx.doi.org/10.2174/1871527313666140917095514] [PMID: 25230234]
[5]
Subramanian, J.; Savage, J.C.; Tremblay, M.È. Synaptic loss in Alzheimer’s disease: Mechanistic insights provided by two-photon in vivo imaging of transgenic mouse models. Front. Cell. Neurosci., 2020, 14, 592607.
[http://dx.doi.org/10.3389/fncel.2020.592607] [PMID: 33408613]
[6]
Nunes-Tavares, N.; Santos, L.E.; Stutz, B.; Brito-Moreira, J.; Klein, W.L.; Ferreira, S.T.; de Mello, F.G. Inhibition of choline acetyltransferase as a mechanism for cholinergic dysfunction induced by amyloid-β peptide oligomers. J. Biol. Chem., 2012, 287(23), 19377-19385.
[http://dx.doi.org/10.1074/jbc.M111.321448] [PMID: 22505713]
[7]
Waldkirch, S.Z.; Luehmann, M.M. The role of glial cells and synapse loss in mouse models of Alzheimer’s disease. Front. Cell. Neurosci., 2018, 287, 19377-19385.
[8]
Ferreira-Vieira, T.H.; Guimaraes, I.M.; Silva, F.R.; Ribeiro, F.M. Alzheimer’s disease: Targeting the cholinergic system. Curr. Neuropharmacol., 2016, 14(1), 101-115.
[http://dx.doi.org/10.2174/1570159X13666150716165726] [PMID: 26813123]
[9]
Gill, S.K.; Bhattacharya, M.; Ferguson, S.S.; Rylett, R.J. Identification of a novel nuclear localization signal common to 69- and 82-kDa human choline acetyltransferase. J. Biol. Chem., 2003, 278(22), 20217-20224.
[http://dx.doi.org/10.1074/jbc.M213153200] [PMID: 12637523]
[10]
Ferguson, S.M.; Bazalakova, M.; Savchenko, V.; Tapia, J.C.; Wright, J.; Blakely, R.D. Lethal impairment of cholinergic neurotransmission in hemicholinium-3-sensitive choline transporter knockout mice. Proc. Natl. Acad. Sci. USA, 2004, 101(23), 8762-8767.
[http://dx.doi.org/10.1073/pnas.0401667101] [PMID: 15173594]
[11]
Rice, M.E. Ascorbate regulation and its neuroprotective role in the brain. Trends Neurosci., 2000, 23(5), 209-216.
[http://dx.doi.org/10.1016/S0166-2236(99)01543-X] [PMID: 10782126]
[12]
Colović, M.B.; Krstić, D.Z.; Lazarević-Pašti, T.D.; Bondžić, A.M.; Vasić, V.M. Acetylcholinesterase inhibitors: Pharmacology and toxicology. Curr. Neuropharmacol., 2013, 11(3), 315-335.
[http://dx.doi.org/10.2174/1570159X11311030006] [PMID: 24179466]
[13]
Wilkinson, D.G.; Francis, P.T.; Schwam, E.; Payne-Parrish, J. Cholinesterase inhibitors used in the treatment of Alzheimer’s disease: The relationship between pharmacological effects and clinical efficacy. Drugs Aging, 2004, 21(7), 453-478.
[http://dx.doi.org/10.2165/00002512-200421070-00004] [PMID: 15132713]
[14]
Pohanka, M. Inhibitors of acetylcholinesterase and butyrylcholinesterase meet immunity. Int. J. Mol. Sci., 2014, 15(6), 9809-9825.
[http://dx.doi.org/10.3390/ijms15069809] [PMID: 24893223]
[15]
Cano, A.; Ettcheto, M.; Chang, J.H.; Barroso, E.; Espina, M.; Kühne, B.A.; Barenys, M.; Auladell, C.; Folch, J.; Souto, E.B.; Camins, A.; Turowski, P.; García, M.L. Dual-drug loaded nanoparticles of Epigallocatechin-3-gallate (EGCG)/Ascorbic acid enhance therapeutic efficacy of EGCG in a APPswe/PS1dE9 Alzheimer’s disease mice model. J. Control. Release, 2019, 301, 62-75.
[http://dx.doi.org/10.1016/j.jconrel.2019.03.010] [PMID: 30876953]
[16]
Cano, A.; Turowski, P.; Ettcheto, M.; Duskey, J.T.; Tosi, G.; Sánchez-López, E.; García, M.L.; Camins, A.; Souto, E.B.; Ruiz, A.; Marquié, M.; Boada, M. Nanomedicine-based technologies and novel biomarkers for the diagnosis and treatment of Alzheimer’s disease: From current to future challenges. J. Nanobiotechnology, 2021, 19(1), 122.
[http://dx.doi.org/10.1186/s12951-021-00864-x] [PMID: 33926475]
[17]
Chen, J.; Li, S.; Shen, Q. Folic acid and cell-penetrating peptide conjugated PLGA-PEG bifunctional nanoparticles for vincristine sulfate delivery. Eur. J. Pharm. Sci., 2012, 47(2), 430-443.
[http://dx.doi.org/10.1016/j.ejps.2012.07.002] [PMID: 22796217]
[18]
Naqvi, S.; Panghal, A.; Flora, S.J.S. Nanotechnology: A promising approach for delivery of neuroprotective drugs. Front. Neurosci., 2020, 14, 494.
[http://dx.doi.org/10.3389/fnins.2020.00494] [PMID: 32581676]
[19]
Gajbhiye, V.; Kumar, P.V.; Sharma, A.; Agarwal, A.; Asthana, A.; Jain, N.K. Dendrimeric nanoarchitectures mediated transdermal and oral delivery of bioactives. Indian J. Pharm. Sci., 2008, 70(4), 431-439.
[http://dx.doi.org/10.4103/0250-474X.44589] [PMID: 20046766]
[20]
Gupta, R.; Sagar, P.; Priyadarshi, N.; Kaul, S.; Sandhir, R.; Rishi, V.; Kumar Singhal, N. Nanotechnology-based approaches for the detection of SARS-CoV-2. Front. Nanotechnol., 2020, 2, 1-14.
[http://dx.doi.org/10.3389/fnano.2020.589832]
[21]
Cheng, Q.; Wei, T.; Farbiak, L.; Johnson, L.T.; Dilliard, S.A.; Siegwart, D.J. Selective organ targeting (SORT) nanoparticles for tissue-specific mRNA delivery and CRISPR-Cas gene editing. Nat. Nanotechnol., 2020, 15(4), 313-320.
[http://dx.doi.org/10.1038/s41565-020-0669-6] [PMID: 32251383]
[22]
Gajbhiye, V.; Jain, N.K. The treatment of Glioblastoma Xenografts by surfactant conjugated dendritic nanoconjugates. Biomaterials, 2011, 32(26), 6213-6225.
[http://dx.doi.org/10.1016/j.biomaterials.2011.04.057] [PMID: 21616528]
[23]
Gajbhiye, V.; Kumar, P.V.; Sharma, A.; Jain, N.K. Novel PEGylated PPI dendritic nanostructures for sustained delivery of anti-inflammatory agent. Curr. Nanosci., 2008, 4(3), 267-277.
[http://dx.doi.org/10.2174/157341308785161136]
[24]
Binda, A.; Murano, C.; Rivolta, I. Innovative therapies and nanomedicine applications for the treatment of Alzheimer’s disease: A state-of-the-art (2017-2020). Int. J. Nanomedicine, 2020, 15, 6113-6135.
[http://dx.doi.org/10.2147/IJN.S231480] [PMID: 32884267]
[25]
Gajbhiye, K.R.; Pawar, A.; Mahadik, K.R.; Gajbhiye, V. PEGylated nanocarriers: A promising tool for targeted delivery to the brain. Colloids Surf. B Biointerfaces, 2020, 187, 110770.
[http://dx.doi.org/10.1016/j.colsurfb.2019.110770] [PMID: 31926790]
[26]
Gajbhiye, K.R.; Gajbhiye, V.; Soni, V. Targeted brain delivery of bioactive molecules using nanocarriers. J. Bioequivalence Bioavailab., 2015, 7(3), 112.
[http://dx.doi.org/10.4172/jbb.1000224]
[27]
Travica, N.; Ried, K.; Hudson, I.; Sali, A.; Scholey, A.; Pipingas, A. The contribution of plasma and brain vitamin C on Age and gender-related cognitive differences: A mini-review of the literature. Front. Integr. Nuerosci., 2020, 14, 47.
[http://dx.doi.org/10.3389/fnint.2020.00047] [PMID: 32973470]
[28]
Figueroa-Méndez, R.; Rivas-Arancibia, S. Vitamin C in health and disease: Its role in the metabolism of cells and redox state in the brain. Front. Physiol., 2015, 6, 397.
[http://dx.doi.org/10.3389/fphys.2015.00397] [PMID: 26779027]
[29]
Harrison, F.E.; May, J.M. Vitamin C function in the brain: Vital role of the ascorbate transporter SVCT2. Free Radic. Biol. Med., 2009, 46(6), 719-730.
[http://dx.doi.org/10.1016/j.freeradbiomed.2008.12.018] [PMID: 19162177]
[30]
Fan, S.; Zheng, Y.; Liu, X.; Fang, W.; Chen, X.; Liao, W.; Jing, X.; Lei, M.; Tao, E.; Ma, Q.; Zhang, X.; Guo, R.; Liu, J. Curcumin-loaded PLGA-PEG nanoparticles conjugated with B6 peptide for potential use in Alzheimer’s disease. Drug Deliv., 2018, 25(1), 1091-1102.
[http://dx.doi.org/10.1080/10717544.2018.1461955] [PMID: 30107760]
[31]
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.
[http://dx.doi.org/10.1016/j.brainres.2008.01.039] [PMID: 18291351]
[32]
Rompicherla, S.K.L.; Arumugam, K.; Bojja, S.L.; Kumar, N.; Rao, C.M. Pharmacokinetic and pharmacodynamic evaluation of nasal liposome and nanoparticle based rivastigmine formulations in acute and chronic models of Alzheimer’s disease. Naunyn Schmiedebergs Arch. Pharmacol., 2021, 394(8), 1737-1755.
[http://dx.doi.org/10.1007/s00210-021-02096-0] [PMID: 34086100]
[33]
Boddu, S.H.S.; Vaishya, R.; Jwala, J.; Vadlapudi, A.; Pal, D.; Mitra, A.K. Preparation and characterization of folate conjugated nanoparticles of doxorubicin using PLGA-PEG-FOL polymer. Med. Chem., 2012, 2, 68-75.
[34]
Danhier, F.; Vroman, B.; Lecouturier, N.; Crokart, N.; Pourcelle, V.; Freichels, H.; Jérôme, C.; Marchand-Brynaert, J.; Feron, O.; Préat, V. Targeting of tumor endothelium by RGD-grafted PLGA-nanoparticles loaded with paclitaxel. J. Control. Release, 2009, 140(2), 166-173.
[http://dx.doi.org/10.1016/j.jconrel.2009.08.011] [PMID: 19699245]
[35]
Choubdar, N.; Avizheh, S. Nanotechnology based delivery systems of drugs currently used to treat Alzheimer’s disease. Nanosci. Nanotechnol. Asia, 2020, 10(3), 228-247.
[http://dx.doi.org/10.2174/2210681209666190228143636]
[36]
Gajbhiye, K.R.; Gajbhiye, V.; Siddiqui, I.A.; Pilla, S.; Soni, V. Ascorbic acid tethered polymeric nanoparticles enable efficient brain delivery of galantamine: An in vitro-in vivo study. Sci. Rep., 2017, 7(1), 11086.
[http://dx.doi.org/10.1038/s41598-017-11611-4] [PMID: 28894228]
[37]
Cheng, K.K.; Yeung, C.F.; Ho, S.W.; Chow, S.F.; Chow, A.H.; Baum, L. Highly stabilized curcumin nanoparticles tested in an in vitro blood-brain barrier model and in Alzheimer’s disease Tg2576 mice. AAPS J., 2013, 15(2), 324-336.
[http://dx.doi.org/10.1208/s12248-012-9444-4] [PMID: 23229335]
[38]
Yang, J.; Lee, C.; Park, J.; Seo, S.; Kim, E.; Song, Y.; Suh, J.; Yoon, H.; Huh, Y.; Haam, S. Antibody conjugated magnetic PLGA nanoparticles for diagnosis and treatment of breast cancer. J. Mater. Chem., 2007, 17(26), 2695-2699.
[http://dx.doi.org/10.1039/b702538f]
[39]
Yang, M.H.; Yoon, K.D.; Chin, Y.W.; Park, J.H.; Kim, S.H.; Kim, Y.C.; Kim, J. Neuroprotective effects of Dioscorea opposita on scopolamine-induced memory impairment in in vivo behavioral tests and in vitro assays. J. Ethnopharmacol., 2009, 121(1), 130-134.
[http://dx.doi.org/10.1016/j.jep.2008.10.010] [PMID: 19007874]
[40]
Patel, S.K.; Gajbhiye, V.; Jain, N.K. Synthesis, characterization and brain targeting potential of paclitaxel loaded thiamine-PPI nanoconjugates. J. Drug Target., 2012, 20(10), 841-849.
[http://dx.doi.org/10.3109/1061186X.2012.719231] [PMID: 22994427]
[41]
Arumugam, K.; Subramanian, G.S.; Mallayasamy, S.R.; Averineni, R.K.; Reddy, M.S.; Udupa, N. A study of rivastigmine liposomes for delivery into the brain through intranasal route. Acta Pharm., 2008, 58(3), 287-297.
[http://dx.doi.org/10.2478/v10007-008-0014-3] [PMID: 19103565]
[42]
Patel, K.B.; Patel, A.V.; Patel, V.J.; Dave, J.B.; Patel, C.N. Quantitative determination of galantamine hydrobromide in pharmaceutical dosage form by RP-High performance liquid chromatography. J. Chem. Pharm. Res., 2010, 2, 36-43.
[43]
Jogani, V.V.; Shah, P.J.; Mishra, P.; Mishra, A.K.; Misra, A.R. Intranasal mucoadhesive microemulsion of tacrine to improve brain targeting. Alzheimer Dis. Assoc. Disord., 2008, 22(2), 116-124.
[http://dx.doi.org/10.1097/WAD.0b013e318157205b] [PMID: 18525282]
[44]
Joshi, S.A.; Chavhan, S.S.; Sawant, K.K. Rivastigmine-loaded PLGA and PBCA nanoparticles: Preparation, optimization, characterization, in vitro and pharmacodynamic studies. Eur. J. Pharm. Biopharm., 2010, 76(2), 189-199.
[http://dx.doi.org/10.1016/j.ejpb.2010.07.007] [PMID: 20637869]
[45]
Bastiat, G.; Plourde, F.; Motulsky, A.; Furtos, A.; Dumont, Y.; Quirion, R.; Fuhrmann, G.; Leroux, J.C. Tyrosine-based rivastigmine-loaded organogels in the treatment of Alzheimer’s disease. Biomaterials, 2010, 31(23), 6031-6038.
[http://dx.doi.org/10.1016/j.biomaterials.2010.04.009] [PMID: 20472283]
[46]
Zhang, P.; Chen, L.; Gu, W.; Xu, Z.; Gao, Y.; Li, Y. In vitro and in vivo evaluation of donepezil-sustained release microparticles for the treatment of Alzheimer’s disease. Biomaterials, 2007, 28(10), 1882-1888.
[http://dx.doi.org/10.1016/j.biomaterials.2006.12.016] [PMID: 17196249]
[47]
Alimohammadi, S.; Salehi, R.; Amini, N.; Davaran, S. Synthesis and physicochemical characterization of biodegradable PLGA-based magnetic nanoparticles containing amoxicillin. Bull. Korean Chem. Soc., 2012, 33(10), 3225-3232.
[http://dx.doi.org/10.5012/bkcs.2012.33.10.3225]
[48]
Lin, G.; Cosimbescu, L.; Karin, N.J.; Tarasevich, B.J. Injectable and thermosensitive PLGA-g-PEG hydrogels containing hydroxyapatite: Preparation, characterization and in vitro release behavior. Biomed. Mater., 2012, 7(2), 024107.
[http://dx.doi.org/10.1088/1748-6041/7/2/024107] [PMID: 22456931]
[49]
Galindo-Rodriguez, S.; Allémann, E.; Fessi, H.; Doelker, E. Physicochemical parameters associated with nanoparticle formation in the salting-out, emulsification-diffusion, and nanoprecipitation methods. Pharm. Res., 2004, 21(8), 1428-1439.
[http://dx.doi.org/10.1023/B:PHAM.0000036917.75634.be] [PMID: 15359578]
[50]
Bilati, U.; Allémann, E.; Doelker, E. Development of a nanoprecipitation method intended for the entrapment of hydrophilic drugs into nanoparticles. Eur. J. Pharm. Sci., 2005, 24(1), 67-75.
[http://dx.doi.org/10.1016/j.ejps.2004.09.011] [PMID: 15626579]
[51]
Afshari, M.; Derakhshandeh, K.; Hosseinzadeh, L. Characterisation, cytotoxicity and apoptosis studies of methotrexate-loaded PLGA and PLGA-PEG nanoparticles. J. Microencapsul., 2014, 31(3), 239-245.
[http://dx.doi.org/10.3109/02652048.2013.834991] [PMID: 24124881]
[52]
Pagar, K.; Vavia, P. Rivastigmine-loaded L-lactide-depsipeptide polymeric nanoparticles: Decisive formulation variable optimization. Sci. Pharm., 2013, 81(3), 865-885.
[http://dx.doi.org/10.3797/scipharm.1211-20] [PMID: 24106679]
[53]
Ravi, G.; Gupta, N.V. Development of solid lipid nanoparticles of rivastigmine tartrate by using full factorial design for the treatment of Alzheimer’s disease. J. Pharm. Sci. Res., 2017, 9, 2447-2452.
[54]
Cooper, D.L.; Harirforoosh, S. Design and optimization of PLGA-based diclofenac loaded nanoparticles. PLoS One, 2014, 9(1), e87326.
[http://dx.doi.org/10.1371/journal.pone.0087326] [PMID: 24489896]
[55]
Ahmed, O.A.A.; Bard-Eldin, S.M.; Ahmed, T.A. Kinetic study of the in vitro release and stability of theophylline floating beads. Int. J. Pharm. Pharm. Sci., 2013, 5, 179-184.
[56]
Mathew, S.T.; Devi, S.G.; Kv, S. Formulation and evaluation of ketorolac tromethamine-loaded albumin microspheres for potential intramuscular administration. AAPS PharmSciTech, 2007, 8(1), 14.
[http://dx.doi.org/10.1208/pt0801014] [PMID: 17408214]
[57]
Carriazo, D.; de Arco, M.; Mertin, C.; Ramos, C.; Rives, V. Influence of the inorganic matrix nature on the sustained release of naproxen. Microporous Mesoporous Mater., 2010, 130(1-3), 229-238.
[http://dx.doi.org/10.1016/j.micromeso.2009.11.014]
[58]
Karewicz, A.; Zasada, K.; Szczubiałka, K.; Zapotoczny, S.; Lach, R.; Nowakowska, M. “Smart” alginate-hydroxypropylcellulose microbeads for controlled release of heparin. Int. J. Pharm., 2010, 385(1-2), 163-169.
[http://dx.doi.org/10.1016/j.ijpharm.2009.10.021] [PMID: 19840839]
[59]
Li, L.; Xiang, D.; Shigdar, S.; Yang, W.; Li, Q.; Lin, J.; Liu, K.; Duan, W. Epithelial cell adhesion molecule aptamer functionalized PLGA-lecithin-curcumin-PEG nanoparticles for targeted drug delivery to human colorectal adenocarcinoma cells. Int. J. Nanomedicine, 2014, 9, 1083-1096.
[PMID: 24591829]
[60]
Huda, N.H.; Gauri, B.; Benson, H.A.E.; Chen, Y. A stability indicating HPLC assay method for analysis of rivastigmine hydrogen tartrate in dual-ligand nanoparticle formulation matrices and cell transport medium. J. Anal. Methods Chem., 2018, 2018, 1841937.
[http://dx.doi.org/10.1155/2018/1841937] [PMID: 29686925]
[61]
Kulkarni, K.S.; Kasture, S.B.; Mengi, S.A. Efficacy study of Prunus amygdalus (almond) nuts in scopolamine-induced amnesia in rats. Int. J. Pharmacol., 2010, 42(3), 168-173.
[http://dx.doi.org/10.4103/0253-7613.66841] [PMID: 20871769]
[62]
Peña, I.D.; Yoon, S.Y.; Kim, H.J.; Park, S.; Hong, E.Y.; Ryu, J.H.; Park, I.H.; Cheong, J.H. Effects of ginseol k-g3, an Rg3-enriched fraction, on scopolamine-induced memory impairment and learning deficit in mice. J. Ginseng Res., 2014, 38(1), 1-7.
[http://dx.doi.org/10.1016/j.jgr.2013.11.003] [PMID: 24558303]

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