{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,31]],"date-time":"2026-10-31T01:34:36Z","timestamp":1793410476341,"version":"4.5.0"},"reference-count":146,"publisher":"MDPI AG","issue":"18","license":[{"start":{"date-parts":[[2021,9,19]],"date-time":"2021-09-19T00:00:00Z","timestamp":1632009600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000038","name":"Natural Sciences and Engineering Research Council of Canada","doi-asserted-by":"publisher","award":["R4036A01"],"award-info":[{"award-number":["R4036A01"]}],"id":[{"id":"10.13039\/501100000038","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Central nervous system (CNS) diseases are the leading causes of death and disabilities in the world. It is quite challenging to treat CNS diseases efficiently because of the blood\u2013brain barrier (BBB). It is a physical barrier with tight junction proteins and high selectivity to limit the substance transportation between the blood and neural tissues. Thus, it is important to understand BBB transport mechanisms for developing novel drug carriers to overcome the BBB. This paper introduces the structure of the BBB and its physiological transport mechanisms. Meanwhile, different strategies for crossing the BBB by using nanomaterial-based drug carriers are reviewed, including carrier-mediated, adsorptive-mediated, and receptor-mediated transcytosis. Since the viral-induced CNS diseases are associated with BBB breakdown, various neurotropic viruses and their mechanisms on BBB disruption are reviewed and discussed, which are considered as an alternative solution to overcome the BBB. Therefore, most recent studies on virus-mimicking nanocarriers for drug delivery to cross the BBB are also reviewed and discussed. On the other hand, the routes of administration of drug-loaded nanocarriers to the CNS have been reviewed. In sum, this paper reviews and discusses various strategies and routes of nano-formulated drug delivery systems across the BBB to the brain, which will contribute to the advanced diagnosis and treatment of CNS diseases.<\/jats:p>","DOI":"10.3390\/ijms221810118","type":"journal-article","created":{"date-parts":[[2021,9,21]],"date-time":"2021-09-21T08:04:23Z","timestamp":1632211463000},"page":"10118","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":95,"title":["Design and Development of Nanomaterial-Based Drug Carriers to Overcome the Blood\u2013Brain Barrier by Using Different Transport Mechanisms"],"prefix":"10.3390","volume":"22","author":[{"given":"Jisu","family":"Song","sequence":"first","affiliation":[{"name":"School of Biomedical Engineering, University of Western Ontario, 1151 Richmond Str., London, ON N6A 5B9, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7858-7927","authenticated-orcid":false,"given":"Chao","family":"Lu","sequence":"additional","affiliation":[{"name":"Department of Chemical and Biochemical Engineering, University of Western Ontario, 1151 Richmond Str., London, ON N6A 5B9, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jerzy","family":"Leszek","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, Wroclaw Medical University, Pasteura 10, 50-367 Wroclaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6875-8008","authenticated-orcid":false,"given":"Jin","family":"Zhang","sequence":"additional","affiliation":[{"name":"School of Biomedical Engineering, University of Western Ontario, 1151 Richmond Str., London, ON N6A 5B9, Canada"},{"name":"Department of Chemical and Biochemical Engineering, University of Western Ontario, 1151 Richmond Str., London, ON N6A 5B9, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,9,19]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1055","DOI":"10.1038\/jcbfm.2015.76","article-title":"Cerebrospinal Fluid Biomarkers of Neurovascular Dysfunction in Mild Dementia and Alzheimer\u2019s Disease","volume":"35","author":"Sweeney","year":"2015","journal-title":"J. Cereb. Blood Flow Metab."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"119491","DOI":"10.1016\/j.biomaterials.2019.119491","article-title":"Nanomaterial-based blood-brain-barrier (BBB) crossing strategies","volume":"224","author":"Xie","year":"2019","journal-title":"Biomaterials"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1156","DOI":"10.1016\/j.bbrc.2016.08.067","article-title":"A critical evaluation of neuroprotective and neurodegenerative MicroRNAs in Alzheimer\u2019s disease","volume":"483","author":"Reddy","year":"2017","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.drup.2015.02.002","article-title":"Overcoming the blood\u2013brain tumor barrier for effective glioblastoma treatment","volume":"19","author":"Wesseling","year":"2015","journal-title":"Drug Resist. Updates"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1602\/neurorx.2.1.3","article-title":"The Blood-Brain Barrier: Bottleneck in Brain Drug Development","volume":"2","author":"Pardridge","year":"2005","journal-title":"NeuroRx"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1016\/j.jconrel.2016.05.044","article-title":"Nanoparticle-mediated brain drug delivery: Overcoming blood\u2013brain barrier to treat neurodegenerative diseases","volume":"235","author":"Saraiva","year":"2016","journal-title":"J. Control. Release"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1038\/nrn1824","article-title":"Astrocyte\u2013endothelial interactions at the blood\u2013brain barrier","volume":"7","author":"Abbott","year":"2006","journal-title":"Nat. Rev. Neurosci."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1016\/j.nbd.2009.07.030","article-title":"Structure and function of the blood\u2013brain barrier","volume":"37","author":"Abbott","year":"2010","journal-title":"Neurobiol. Dis."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"e1153568","DOI":"10.1080\/21688370.2016.1153568","article-title":"Nanoparticle transport across the blood brain barrier","volume":"4","author":"Grabrucker","year":"2016","journal-title":"Tissue Barriers"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"264","DOI":"10.1016\/j.jconrel.2011.08.017","article-title":"Transport of drugs across the blood\u2013brain barrier by nanoparticles","volume":"161","author":"Wohlfart","year":"2012","journal-title":"J. Control. Release"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"282","DOI":"10.1016\/j.tim.2012.03.009","article-title":"Viral disruption of the blood\u2013brain barrier","volume":"20","author":"Spindler","year":"2012","journal-title":"Trends Microbiol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"314","DOI":"10.1039\/C7BM01012E","article-title":"Uptake and transcytosis of functionalized superparamagnetic iron oxide nanoparticles in an in vitro blood brain barrier model","volume":"6","author":"Ivask","year":"2018","journal-title":"Biomater. Sci."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1093\/toxsci\/kfx079","article-title":"From the Cover: Comparative Proteomics Reveals Silver Nanoparticles Alter Fatty Acid Metabolism and Amyloid Beta Clearance for Neuronal Apoptosis in a Triple Cell Coculture Model of the Blood\u2013Brain Barrier","volume":"158","author":"Lin","year":"2017","journal-title":"Toxicol. Sci."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"701","DOI":"10.1016\/j.addr.2011.12.006","article-title":"Polymeric nanoparticles for drug delivery to the central nervous system","volume":"64","author":"Patel","year":"2012","journal-title":"Adv. Drug Deliv. Rev."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1435","DOI":"10.7150\/thno.22482","article-title":"Targeted Delivery of Functionalized Upconversion Nanoparticles for Externally Triggered Photothermal\/Photodynamic Therapies of Brain Glioblastoma","volume":"8","author":"Tsai","year":"2018","journal-title":"Theranostics"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"2264","DOI":"10.7150\/thno.23734","article-title":"Localized delivery of curcumin into brain with polysorbate 80-modified cerasomes by ultrasound-targeted microbubble destruction for improved Parkinson\u2019s disease therapy","volume":"8","author":"Zhang","year":"2018","journal-title":"Theranostics"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"835","DOI":"10.1002\/ana.22318","article-title":"Glut1\/SLC2A1 is crucial for the development of the blood-brain barrier in vivo","volume":"68","author":"Zheng","year":"2010","journal-title":"Ann. Neurol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"2523","DOI":"10.1007\/s11095-012-0966-3","article-title":"Design, synthesis and brain uptake of LAT1-targeted amino acid prodrugs of dopamine","volume":"30","author":"Peura","year":"2013","journal-title":"Pharm. Res."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"634","DOI":"10.1053\/j.gastro.2011.11.028","article-title":"Hepatitis C Virus Infects the Endothelial Cells of the Blood-Brain Barrier","volume":"142","author":"Fletcher","year":"2012","journal-title":"Gastroenterology"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"8978","DOI":"10.1128\/JVI.00314-08","article-title":"Matrix Metalloproteinase 9 Facilitates West Nile Virus Entry into the Brain","volume":"82","author":"Wang","year":"2008","journal-title":"J. Virol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1186\/1742-2094-9-12","article-title":"Japanese encephalitis virus induces matrix metalloproteinase-9 expression via a ROS\/c-Src\/PDGFR\/PI3K\/Akt\/MAPKs-dependent AP-1 pathway in rat brain astrocytes","volume":"9","author":"Yang","year":"2012","journal-title":"J. Neuroinflamm."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"859","DOI":"10.1099\/0022-1317-72-4-859","article-title":"Breakdown of the blood-brain barrier during dengue virus infection of mice","volume":"72","author":"Chaturvedi","year":"1991","journal-title":"J. Gen. Virol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"214","DOI":"10.3389\/fmicb.2020.00214","article-title":"The Mechanism of the Zika Virus Crossing the Placental Barrier and the Blood-Brain Barrier","volume":"11","author":"Chiu","year":"2020","journal-title":"Front. Microbiol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/s41467-020-15562-9","article-title":"Characterization of spike glycoprotein of SARS-CoV-2 on virus entry and its immune cross-reactivity with SARS-CoV","volume":"11","author":"Ou","year":"2020","journal-title":"Nat. Commun."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"562","DOI":"10.1038\/s41564-020-0688-y","article-title":"Functional assessment of cell entry and receptor usage for SARS-CoV-2 and other lineage B betacoronaviruses","volume":"5","author":"Letko","year":"2020","journal-title":"Nat. Microbiol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1016\/j.cell.2020.02.052","article-title":"SARS-CoV-2 Cell Entry Depends on ACE2 and TMPRSS2 and Is Blocked by a Clinically Proven Protease Inhibitor","volume":"181","author":"Hoffmann","year":"2020","journal-title":"Cell"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1260","DOI":"10.1126\/science.abb2507","article-title":"Cryo-EM structure of the 2019-nCoV spike in the prefusion conformation","volume":"367","author":"Wrapp","year":"2020","journal-title":"Science"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1016\/j.virusres.2014.09.011","article-title":"Human coronaviruses: Viral and cellular factors involved in neuroinvasiveness and neuropathogenesis","volume":"194","author":"Desforges","year":"2014","journal-title":"Virus Res."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1392","DOI":"10.1128\/CDLI.9.6.1392-1395.2002","article-title":"In Vitro Detection of Apoptosis in Monocytes\/Macrophages Infected with Human Coronavirus","volume":"9","author":"Collins","year":"2002","journal-title":"Clin. Vaccine Immunol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"8275","DOI":"10.1073\/pnas.0408589102","article-title":"From The Cover: Development of a transgenic mouse model susceptible to human coronavirus 229E","volume":"102","author":"Lassnig","year":"2005","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"415","DOI":"10.1084\/jem.20050828","article-title":"Multiple organ infection and the pathogenesis of SARS","volume":"202","author":"Gu","year":"2005","journal-title":"J. Exp. Med."},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Nicholls, J.M., Butany, J., Poon, L.L.M., Chan, K.H., Beh, S.L., Poutanen, S., Peiris, J.S.M., and Wong, M. (2006). Time Course and Cellular Localization of SARS-CoV Nucleoprotein and RNA in Lungs from Fatal Cases of SARS. PLoS Med., 3.","DOI":"10.1371\/journal.pmed.0030027"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"97","DOI":"10.3389\/fphar.2014.00097","article-title":"HSV-1 and Alzheimer\u2019s disease: More than a hypothesis","volume":"5","author":"Piacentini","year":"2014","journal-title":"Front. Pharmacol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"274","DOI":"10.1016\/j.neulet.2004.06.064","article-title":"Increased presence of matrix metalloproteinases 2 and 9 in short- and long-term experimental herpes simplex virus encephalitis","volume":"368","author":"Wagner","year":"2004","journal-title":"Neurosci. Lett."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1016\/j.biomaterials.2014.10.068","article-title":"Enhanced BBB permeability of osmotically active poly(mannitol-co-PEI) modified with rabies virus glycoprotein via selective stimulation of caveolar endocytosis for RNAi therapeutics in Alzheimer\u2019s disease","volume":"38","author":"Park","year":"2015","journal-title":"Biomaterials"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"9398","DOI":"10.1128\/JVI.00954-09","article-title":"Mouse Adenovirus Type 1-Induced Breakdown of the Blood-Brain Barrier","volume":"83","author":"Gralinski","year":"2009","journal-title":"J. Virol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1219","DOI":"10.1128\/JVI.72.2.1219-1223.1998","article-title":"Distribution of Mouse Adenovirus Type 1 in Intraperitoneally and Intranasally Infected Adult Outbred Mice","volume":"72","author":"Kajon","year":"1998","journal-title":"J. Virol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"307","DOI":"10.1016\/j.virol.2009.05.025","article-title":"Mouse adenovirus type 1 infection of macrophages","volume":"390","author":"Ashley","year":"2009","journal-title":"Virology"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1007\/s13365-013-0187-5","article-title":"Theiler\u2019s murine encephalomyelitis virus as an experimental model system to study the mechanism of blood-brain barrier disruption","volume":"20","author":"Johnson","year":"2014","journal-title":"J. Neurovirol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"255","DOI":"10.1146\/annurev-virology-092917-043439","article-title":"Flaviviruses and the Central Nervous System: Revisiting Neuropathological Concepts","volume":"5","author":"Maximova","year":"2018","journal-title":"Annu. Rev. Virol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"839","DOI":"10.1016\/S1474-4422(18)30316-8","article-title":"Herpes viruses and Alzheimer\u2019s disease: New evidence in the debate","volume":"17","author":"Balin","year":"2018","journal-title":"Lancet Neurol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"525","DOI":"10.3389\/fmicb.2019.00525","article-title":"Pathways Exploited by Flaviviruses to Counteract the Blood-Brain Barrier and Invade the Central Nervous System","volume":"10","author":"Meuren","year":"2019","journal-title":"Front. Microbiol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"8824","DOI":"10.1128\/JVI.78.16.8824-8834.2004","article-title":"Human Respiratory Coronavirus OC43: Genetic Stability and Neuroinvasion","volume":"78","author":"Jacomy","year":"2004","journal-title":"J. Virol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"228","DOI":"10.1016\/j.virusres.2007.06.016","article-title":"Activation of human monocytes after infection by human coronavirus 229E","volume":"130","author":"Desforges","year":"2007","journal-title":"Virus Res."},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Singh, S.K., and Ruzek, D. (2013). Neuroviral Infections: RNA Viruses and Retroviruses, CRC.","DOI":"10.1201\/b13908"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"3338","DOI":"10.1128\/JVI.73.4.3338-3350.1999","article-title":"Acute and Persistent Infection of Human Neural Cell Lines by Human Coronavirus OC43","volume":"73","author":"Arbour","year":"1999","journal-title":"J. Virol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"995","DOI":"10.1021\/acschemneuro.0c00122","article-title":"Evidence of the COVID-19 Virus Targeting the CNS: Tissue Distribution, Host\u2013Virus Interaction, and Proposed Neurotropic Mechanisms","volume":"11","author":"Baig","year":"2020","journal-title":"ACS Chem. Neurosci."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"325","DOI":"10.1016\/j.chom.2020.02.001","article-title":"Genome Composition and Divergence of the Novel Coronavirus (2019-nCoV) Originating in China","volume":"27","author":"Wu","year":"2020","journal-title":"Cell Host Microbe"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"552","DOI":"10.1002\/jmv.25728","article-title":"The neuroinvasive potential of SARS-CoV2 may play a role in the respiratory failure of COVID-19 patients","volume":"92","author":"Li","year":"2020","journal-title":"J. Med Virol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"1764","DOI":"10.1111\/ene.14277","article-title":"Does SARS-Cov-2 invade the brain? Translational lessons from animal models","volume":"27","author":"Natoli","year":"2020","journal-title":"Eur. J. Neurol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"1482","DOI":"10.1111\/j.1471-4159.2008.05723.x","article-title":"Angiotensin-converting enzyme 2 in the brain: Properties and future directions","volume":"107","author":"Xia","year":"2008","journal-title":"J. Neurochem."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"497","DOI":"10.1016\/S0140-6736(20)30183-5","article-title":"Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China","volume":"395","author":"Huang","year":"2020","journal-title":"Lancet"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"1491","DOI":"10.1007\/s00701-020-04374-x","article-title":"SARS-CoV-2 can induce brain and spine demyelinating lesions","volume":"162","author":"Zanin","year":"2020","journal-title":"Acta Neurochir."},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"Zhao, K., Huang, J., Dai, D., Feng, Y., Liu, L., and Nie, S. (2020). Acute myelitis after SARS-CoV-2 infection: A case report. MedRxiv.","DOI":"10.1101\/2020.03.16.20035105"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"699","DOI":"10.1002\/jmv.25915","article-title":"Central Nervous System Involvement by Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2)","volume":"92","author":"Bryce","year":"2020","journal-title":"J. Med Virol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"128","DOI":"10.1016\/j.bbi.2020.05.002","article-title":"SARS-CoV-2: \u201cThree-steps\u201d infection model and CSF diagnostic implication","volume":"87","author":"Panciani","year":"2020","journal-title":"Brain Behav. Immun."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"869","DOI":"10.1016\/j.idc.2019.07.001","article-title":"Severe Acute Respiratory Syndrome","volume":"33","author":"Hui","year":"2019","journal-title":"Infect. Dis. Clin. N. Am."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"7264","DOI":"10.1128\/JVI.00737-08","article-title":"Severe Acute Respiratory Syndrome Coronavirus Infection Causes Neuronal Death in the Absence of Encephalitis in Mice Transgenic for Human ACE2","volume":"82","author":"Netland","year":"2008","journal-title":"J. Virol."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"4195","DOI":"10.1016\/j.biomaterials.2009.02.051","article-title":"Brain-targeting gene delivery and cellular internalization mechanisms for modified rabies virus glycoprotein RVG29 nanoparticles","volume":"30","author":"Liu","year":"2009","journal-title":"Biomaterials"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1038\/nrmicro2260","article-title":"The cell biology of rabies virus: Using stealth to reach the brain","volume":"8","author":"Schnell","year":"2010","journal-title":"Nat. Rev. Microbiol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"198","DOI":"10.1016\/j.brainres.2007.10.052","article-title":"Minocycline and hypothermia for reperfusion injury after focal cerebral ischemia in the rat\u2014Effects on BBB breakdown and MMP expression in the acute and subacute phase","volume":"1188","author":"Nagel","year":"2008","journal-title":"Brain Res."},{"key":"ref_62","doi-asserted-by":"crossref","unstructured":"Ayala-Nunez, N.V., and Gaudin, R. (2020). A viral journey to the brain: Current considerations and future developments. PLOS Pathog., 16.","DOI":"10.1371\/journal.ppat.1008434"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"2131","DOI":"10.1021\/am405219u","article-title":"In Vitro and in Vivo Studies on the Transport of PEGylated Silica Nanoparticles across the Blood\u2013Brain Barrier","volume":"6","author":"Liu","year":"2014","journal-title":"ACS Appl. Mater. Interfaces"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"274","DOI":"10.1016\/j.colsurfb.2008.07.004","article-title":"Biodistribution of colloidal gold nanoparticles after intravenous administration: Effect of particle size","volume":"66","author":"Sonavane","year":"2008","journal-title":"Colloids Surf. B Biointerfaces"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1016\/j.nano.2016.08.029","article-title":"Efficacy of NGR peptide-modified PEGylated quantum dots for crossing the blood\u2013brain barrier and targeted fluorescence imaging of glioma and tumor vasculature","volume":"13","author":"Huang","year":"2017","journal-title":"Nanomed. Nanotechnol. Biol. Med."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"2134","DOI":"10.1021\/nn404872e","article-title":"Dendrimer Brain Uptake and Targeted Therapy for Brain Injury in a Large Animal Model of Hypothermic Circulatory Arrest","volume":"8","author":"Mishra","year":"2014","journal-title":"ACS Nano"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"11751","DOI":"10.1073\/pnas.1304504110","article-title":"Highly penetrative, drug-loaded nanocarriers improve treatment of glioblastoma","volume":"110","author":"Zhou","year":"2013","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"454","DOI":"10.1016\/j.ijbiomac.2014.08.052","article-title":"Chitosan as a suitable nanocarrier material for anti-Alzheimer drug delivery","volume":"72","author":"Sarvaiya","year":"2015","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1016\/j.jiec.2019.01.021","article-title":"Nanotherapeutics engineered to cross the blood-brain barrier for advanced drug delivery to the central nervous system","volume":"73","author":"Kim","year":"2019","journal-title":"J. Ind. Eng. Chem."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1016\/j.jconrel.2017.05.019","article-title":"Recent advancements in liposomes targeting strategies to cross blood-brain barrier (BBB) for the treatment of Alzheimer\u2019s disease","volume":"260","author":"Agrawal","year":"2017","journal-title":"J. Control. Release"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"837","DOI":"10.3109\/1061186X.2011.589435","article-title":"Brain-targeted delivery of paclitaxel using glutathione-coated nanoparticles for brain cancers","volume":"19","author":"Geldenhuys","year":"2011","journal-title":"J. Drug Target."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"497","DOI":"10.3109\/10837450.2014.892130","article-title":"Brain-targeted delivery of doxorubicin using glutathione-coated nanoparticles for brain cancers","volume":"20","author":"Geldenhuys","year":"2015","journal-title":"Pharm. Dev. Technol."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"635","DOI":"10.1023\/A:1022482604276","article-title":"Blood-Brain Barrier Carrier-Mediated Transport and Brain Metabolism of Amino Acids","volume":"23","author":"Pardridge","year":"1998","journal-title":"Neurochem. Res."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1002\/(SICI)1098-1136(199709)21:1<2::AID-GLIA2>3.0.CO;2-C","article-title":"Glucose transporter proteins in brain: Delivery of glucose to neurons and glia","volume":"21","author":"Vannucci","year":"1997","journal-title":"Glia"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"518","DOI":"10.1016\/j.biomaterials.2013.09.094","article-title":"Nanoparticles of 2-deoxy-d-glucose functionalized poly(ethylene glycol)-co-poly(trimethylene carbonate) for dual-targeted drug delivery in glioma treatment","volume":"35","author":"Jiang","year":"2014","journal-title":"Biomaterials"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1016\/j.jconrel.2014.03.006","article-title":"The role of glucose transporters in the distribution of p-aminophenyl-\u03b1-d-mannopyranoside modified liposomes within mice brain","volume":"182","author":"Du","year":"2014","journal-title":"J. Control. Release"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"505","DOI":"10.1016\/j.ejpb.2012.12.020","article-title":"Liposomes modified with P-aminophenyl-\u03b1-d-mannopyranoside: A carrier for targeting cerebral functional regions in mice","volume":"84","author":"Hao","year":"2013","journal-title":"Eur. J. Pharm. Biopharm."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.chemphyslip.2015.03.003","article-title":"p-Aminophenyl-\u03b1-d-mannopyranoside engineered lipidic nanoparticles for effective delivery of docetaxel to brain","volume":"188","author":"Singh","year":"2015","journal-title":"Chem. Phys. Lipids"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"32681","DOI":"10.18632\/oncotarget.5354","article-title":"A nanostructure of functional targeting epirubicin liposomes dually modified with aminophenyl glucose and cyclic pentapeptide used for brain glioblastoma treatment","volume":"6","author":"Zhang","year":"2015","journal-title":"Oncotarget"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"831","DOI":"10.1016\/j.cclet.2010.12.056","article-title":"Design, synthesis and preliminary bio-evaluation of glucose\u2013cholesterol derivatives as ligands for brain targeting liposomes","volume":"22","author":"Lei","year":"2011","journal-title":"Chin. Chem. Lett."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"536","DOI":"10.3109\/10611861003587235","article-title":"In vitro and in vivo investigation of glucose-mediated brain-targeting liposomes","volume":"18","author":"Qin","year":"2010","journal-title":"J. Drug Target."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"163","DOI":"10.2147\/IJN.S23771","article-title":"Investigation of glucose-modified liposomes using polyethylene glycols with different chain lengths as the linkers for brain targeting","volume":"7","author":"Xie","year":"2012","journal-title":"Int. J. Nanomed."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1016\/j.biomaterials.2015.09.041","article-title":"Functionalized nanocarrier combined seizure-specific vector with P-glycoprotein modulation property for antiepileptic drug delivery","volume":"74","author":"Liu","year":"2016","journal-title":"Biomaterials"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1016\/j.colsurfb.2015.04.049","article-title":"Targeting of AIDS related encephalopathy using phenylalanine anchored lipidic nanocarrier","volume":"131","author":"Vyas","year":"2015","journal-title":"Colloids Surf. B Biointerfaces"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"1562","DOI":"10.1208\/s12249-014-0165-0","article-title":"Brain-Targeted Delivery of Docetaxel by Glutathione-Coated Nanoparticles for Brain Cancer","volume":"15","author":"Grover","year":"2014","journal-title":"AAPS PharmSciTech"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"388","DOI":"10.1016\/j.nano.2012.08.004","article-title":"\u03b2-Hydroxybutyric acid grafted solid lipid nanoparticles: A novel strategy to improve drug delivery to brain","volume":"9","author":"Venishetty","year":"2013","journal-title":"Nanomed. Nanotechnol. Biol. Med."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"3137","DOI":"10.1007\/s11095-015-1677-3","article-title":"Dual Drug Delivery Using Lactic Acid Conjugated SLN for Effective Management of Neurocysticercosis","volume":"32","author":"Devi","year":"2015","journal-title":"Pharm. Res."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"7233","DOI":"10.1073\/pnas.81.22.7233","article-title":"Identification and characterization of the glucose transporter of the blood-brain barrier by cytochalasin B binding and immunological reactivity","volume":"81","author":"Dick","year":"1984","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"299","DOI":"10.1016\/0006-8993(85)90039-3","article-title":"Regional comparisons of brain glucose influx","volume":"326","author":"LaManna","year":"1985","journal-title":"Brain Res."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"693","DOI":"10.1042\/bj3580693","article-title":"Molecular events involved in up-regulating human Na+-independent neutral amino acid transporter LAT1 during T-cell activation","volume":"358","author":"Nii","year":"2001","journal-title":"Biochem. J."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"497","DOI":"10.1211\/0022357011775794","article-title":"Molecular and functional identification of large neutral amino acid transporters LAT1 and LAT2 and their pharmacological relevance at the blood-brain barrier","volume":"53","author":"Kido","year":"2001","journal-title":"J. Pharm. Pharmacol."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1080\/10717540600559510","article-title":"Targeting the Cerebrovascular Large Neutral Amino Acid Transporter (LAT1) Isoform Using a Novel Disulfide-Based Brain Drug Delivery System","volume":"14","author":"Killian","year":"2007","journal-title":"Drug Deliv."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"1857","DOI":"10.1021\/mp2001878","article-title":"Large Amino Acid Transporter 1 (LAT1) Prodrugs of Valproic Acid: New Prodrug Design Ideas for Central Nervous System Delivery","volume":"8","author":"Peura","year":"2011","journal-title":"Mol. Pharm."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1111\/j.1440-1827.2008.02319.x","article-title":"L-type amino-acid transporter 1 as a novel biomarker for high-grade malignancy in prostate cancer","volume":"59","author":"Sakata","year":"2009","journal-title":"Pathol. Int."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"493","DOI":"10.1227\/01.neu.0000316018.51292.19","article-title":"Enhanced tumor growth elicited by L-type amino acid transporter 1 in human malignant glioma cells","volume":"62","author":"Kobayashi","year":"2008","journal-title":"Neurosurgery"},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"277","DOI":"10.1016\/S0169-409X(98)00084-2","article-title":"Carrier-mediated or specialized transport of drugs across the blood\u2013brain barrier","volume":"36","author":"Tsuji","year":"1999","journal-title":"Adv. Drug Deliv. Rev."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1016\/0169-409X(95)00003-P","article-title":"Transport of small molecules through the blood-brain barrier: Biology and methodology","volume":"15","author":"Pardridge","year":"1995","journal-title":"Adv. Drug Deliv. Rev."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"370","DOI":"10.1006\/bbrc.1995.2786","article-title":"cDNA Cloning and Functional Characterization of Rat Intestinal Monocarboxylate Transporter","volume":"217","author":"Takanaga","year":"1995","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"E207","DOI":"10.1152\/ajpendo.1997.273.1.E207","article-title":"Expression of monocarboxylate transporter MCT1 by brain endothelium and glia in adult and suckling rats","volume":"273","author":"Gerhart","year":"1997","journal-title":"Am. J. Physiol.-Endocrinol. Metab."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"1513","DOI":"10.2217\/nnm-2018-0139","article-title":"Nanoparticle crossing of blood\u2013brain barrier: A road to new therapeutic approaches to central nervous system diseases","volume":"13","year":"2018","journal-title":"Nanomedicine"},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"1438","DOI":"10.1021\/ja309812z","article-title":"Nanoparticle Adhesion to the Cell Membrane and Its Effect on Nanoparticle Uptake Efficiency","volume":"135","author":"Lesniak","year":"2013","journal-title":"J. Am. Chem. Soc."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"455","DOI":"10.1208\/s12248-008-9055-2","article-title":"CNS Delivery Via Adsorptive Transcytosis","volume":"10","author":"Ghinea","year":"2008","journal-title":"AAPS J."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1007\/s40263-016-0405-9","article-title":"Crossing the Blood\u2013Brain Barrier: Recent Advances in Drug Delivery to the Brain","volume":"31","author":"Patel","year":"2017","journal-title":"CNS Drugs"},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1080\/10611860600650086","article-title":"Endocytosis at the blood\u2013brain barrier: From basic understanding to drug delivery strategies","volume":"14","author":"Smith","year":"2006","journal-title":"J. Drug Target."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"1735","DOI":"10.2217\/nnm.15.29","article-title":"PEG-g-chitosan nanoparticles functionalized with the monoclonal antibody OX26 for brain drug targeting","volume":"10","author":"Monsalve","year":"2015","journal-title":"Nanomedicine"},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"1170","DOI":"10.1016\/j.biomaterials.2012.09.047","article-title":"Brain-targeted delivery of protein using chitosan- and RVG peptide-conjugated, pluronic-based nano-carrier","volume":"34","author":"Kim","year":"2013","journal-title":"Biomaterials"},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"420","DOI":"10.1002\/ijc.22296","article-title":"Aclarubicin-loaded cationic albumin-conjugated pegylated nanoparticle for glioma chemotherapy in rats","volume":"120","author":"Lu","year":"2007","journal-title":"Int. J. Cancer"},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1016\/j.ijpharm.2018.11.035","article-title":"\u2018Dendrimer-Cationized-Albumin\u2019 encrusted polymeric nanoparticle improves BBB penetration and anticancer activity of doxorubicin","volume":"555","author":"Muniswamy","year":"2019","journal-title":"Int. J. Pharm."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"71","DOI":"10.2174\/157341311794480291","article-title":"Cationized Albumin Conjugated Solid Lipid Nanoparticles as Vectors for Brain Delivery of an Anti-Cancer Drug","volume":"7","author":"Agarwal","year":"2011","journal-title":"Curr. Nanosci."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1016\/j.ijpharm.2011.09.039","article-title":"Cationic ligand appended nanoconstructs: A prospective strategy for brain targeting","volume":"421","author":"Agarwal","year":"2011","journal-title":"Int. J. Pharm."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"350","DOI":"10.1039\/C1NJ20444K","article-title":"The biodistribution of maltotriose modified poly(propylene imine) (PPI) dendrimers conjugated with fluorescein\u2014Proofs of crossing blood\u2013brain\u2013barrier","volume":"36","author":"Janaszewska","year":"2012","journal-title":"New J. Chem."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"355102","DOI":"10.1088\/0957-4484\/21\/35\/355102","article-title":"Characterization of endocytosis and exocytosis of cationic nanoparticles in airway epithelium cells","volume":"21","author":"Dombu","year":"2010","journal-title":"Nanotechnology"},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"1203","DOI":"10.1111\/cbdd.12586","article-title":"Cationic Albumin-Conjugated Chelating Agent as a Novel Brain Drug Delivery System in Neurodegeneration","volume":"86","author":"Kamalinia","year":"2015","journal-title":"Chem. Biol. Drug Des."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"551","DOI":"10.1016\/j.nano.2011.05.004","article-title":"Functionalization of liposomes with ApoE-derived peptides at different density affects cellular uptake and drug transport across a blood-brain barrier model","volume":"7","author":"Re","year":"2011","journal-title":"Nanomed. Nanotechnol. Biol. Med."},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1016\/j.ejpb.2008.08.021","article-title":"Transferrin- and transferrin-receptor-antibody-modified nanoparticles enable drug delivery across the blood\u2013brain barrier (BBB)","volume":"71","author":"Ulbrich","year":"2009","journal-title":"Eur. J. Pharm. Biopharm."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"299","DOI":"10.1016\/j.ejps.2005.03.008","article-title":"Targeting liposomes with protein drugs to the blood\u2013brain barrier in vitro","volume":"25","author":"Visser","year":"2005","journal-title":"Eur. J. Pharm. Sci."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1016\/j.ijpharm.2009.04.035","article-title":"Characterization of endocytosis of transferrin-coated PLGA nanoparticles by the blood\u2013brain barrier","volume":"379","author":"Chang","year":"2009","journal-title":"Int. J. Pharm."},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"134","DOI":"10.1016\/j.jconrel.2015.06.002","article-title":"PLGA nanoparticles prepared by nano-emulsion templating using low-energy methods as efficient nanocarriers for drug delivery across the blood\u2013brain barrier","volume":"211","author":"Fornaguera","year":"2015","journal-title":"J. Control. Release"},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"3304","DOI":"10.1021\/nn300240p","article-title":"Receptor-Mediated Delivery of Magnetic Nanoparticles across the Blood\u2013Brain Barrier","volume":"6","author":"Qiao","year":"2012","journal-title":"ACS Nano"},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"5980","DOI":"10.1039\/C6TB01329E","article-title":"Tailored mesoporous silica nanosystem with enhanced permeability of the blood\u2013brain barrier to antagonize glioblastoma","volume":"4","author":"You","year":"2016","journal-title":"J. Mater. Chem. B"},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"387","DOI":"10.1002\/bit.21764","article-title":"GDNF fusion protein for targeted-drug delivery across the human blood\u2013brain barrier","volume":"100","author":"Boado","year":"2008","journal-title":"Biotechnol. Bioeng."},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"125","DOI":"10.3109\/10611861003734001","article-title":"Targeting the insulin receptor: Nanoparticles for drug delivery across the blood\u2013brain barrier (BBB)","volume":"19","author":"Ulbrich","year":"2011","journal-title":"J. Drug Target."},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"7748","DOI":"10.1016\/j.biomaterials.2010.06.053","article-title":"Transferrin-conjugated nanoparticles of Poly(lactide)-d-\u03b1-Tocopheryl polyethylene glycol succinate diblock copolymer for targeted drug delivery across the blood\u2013brain barrier","volume":"31","author":"Gan","year":"2010","journal-title":"Biomaterials"},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"9999","DOI":"10.1021\/acsnano.6b04268","article-title":"Blood\u2013Brain-Barrier-Penetrating Albumin Nanoparticles for Biomimetic Drug Delivery via Albumin-Binding Protein Pathways for Antiglioma Therapy","volume":"10","author":"Lin","year":"2016","journal-title":"ACS Nano"},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"8583","DOI":"10.1021\/nn402662d","article-title":"Cyclic RGD-Linked Polymeric Micelles for Targeted Delivery of Platinum Anticancer Drugs to Glioblastoma through the Blood\u2013Brain Tumor Barrier","volume":"7","author":"Miura","year":"2013","journal-title":"ACS Nano"},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1016\/j.addr.2007.03.008","article-title":"shRNA and siRNA delivery to the brain","volume":"59","author":"Pardridge","year":"2007","journal-title":"Adv. Drug Deliv. Rev."},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1002\/med.10008","article-title":"Transferrin\/transferrin receptor-mediated drug delivery","volume":"22","author":"Li","year":"2002","journal-title":"Med. Res. Rev."},{"key":"ref_128","doi-asserted-by":"crossref","unstructured":"Wong, K.H., Riaz, M.K., Xie, Y., Zhang, X., Liu, Q., Chen, H., Bian, Z., Chen, X., Lu, A., and Yang, Z. (2019). Review of Current Strategies for Delivering Alzheimer\u2019s Disease Drugs across the Blood-Brain Barrier. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20020381"},{"key":"ref_129","doi-asserted-by":"crossref","unstructured":"Zhang, Y., Lu, C., and Zhang, J. (2021). Lactoferrin and Its Detection Methods: A Review. Nutrients, 13.","DOI":"10.3390\/nu13082492"},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"1771","DOI":"10.1111\/j.1471-4159.1985.tb07167.x","article-title":"Human Blood\u2014Brain Barrier Insulin Receptor","volume":"44","author":"Pardridge","year":"1985","journal-title":"J. Neurochem."},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"1605563","DOI":"10.1002\/adma.201605563","article-title":"Rabies Virus-Inspired Silica-Coated Gold Nanorods as a Photothermal Therapeutic Platform for Treating Brain Tumors","volume":"29","author":"Lee","year":"2017","journal-title":"Adv. Mater."},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1007\/s13365-015-0397-0","article-title":"Microglia-derived HIV Nef+ exosome impairment of the blood\u2013brain barrier is treatable by nanomedicine-based delivery of Nef peptides","volume":"22","author":"Raymond","year":"2016","journal-title":"J. Neurovirol."},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"263","DOI":"10.2174\/1566523217666161121105717","article-title":"Releasing of Herpes Simplex Virus Carrying NGF in Subarachnoid Space Promotes the Functional Repair in Spinal Cord Injured Rats","volume":"16","author":"Chen","year":"2016","journal-title":"Curr. Gene Ther."},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"586","DOI":"10.1227\/01.NEU.0000290907.30814.42","article-title":"Vascular endothelial growth factor gene-transferred bone marrow stromal cells engineered with a herpes simplex virus type 1 vector can improve neurological deficits and reduce infarction volume in rat brain ischemia","volume":"61","author":"Miki","year":"2007","journal-title":"Neurosurgery"},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"741","DOI":"10.3233\/JAD-130977","article-title":"Titers of Herpes Simplex Virus Type 1 Antibodies Positively Correlate with Grey Matter Volumes in Alzheimer\u2019s Disease","volume":"38","author":"Mancuso","year":"2013","journal-title":"J. Alzheimer\u2019s Dis."},{"key":"ref_136","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/srep12497","article-title":"Tailored delivery of analgesic ziconotide across a blood brain barrier model using viral nanocontainers","volume":"5","author":"Anand","year":"2015","journal-title":"Sci. Rep."},{"key":"ref_137","doi-asserted-by":"crossref","first-page":"640","DOI":"10.1016\/j.addr.2011.11.010","article-title":"Modern methods for delivery of drugs across the blood\u2013brain barrier","volume":"64","author":"Chen","year":"2012","journal-title":"Adv. Drug Deliv. Rev."},{"key":"ref_138","doi-asserted-by":"crossref","first-page":"1759","DOI":"10.1007\/s11095-007-9379-0","article-title":"Blood\u2013Brain Barrier Transport of Therapeutics via Receptor-Mediation","volume":"24","author":"Jones","year":"2007","journal-title":"Pharm. Res."},{"key":"ref_139","doi-asserted-by":"crossref","first-page":"194","DOI":"10.1002\/ana.22421","article-title":"The blood-spinal cord barrier: Morphology and Clinical Implications","volume":"70","author":"Bartanusz","year":"2011","journal-title":"Ann. Neurol."},{"key":"ref_140","doi-asserted-by":"crossref","first-page":"789","DOI":"10.3233\/JAD-122308","article-title":"Sex and ApoE Genotype Differences in Treatment Response to Two Doses of Intranasal Insulin in Adults with Mild Cognitive Impairment or Alzheimer\u2019s Disease","volume":"35","author":"Claxton","year":"2013","journal-title":"J. Alzheimer\u2019s Dis."},{"key":"ref_141","doi-asserted-by":"crossref","unstructured":"Sonvico, F., Clementino, A., Buttini, F., Colombo, G., Pescina, S., Stanis\u00e7uaski Guterres, S., Raffin Pohlmann, A., and Nicoli, S. (2018). Surface-Modified Nanocarriers for Nose-to-Brain Delivery: From Bioadhesion to Targeting. Pharmaceutics, 10.","DOI":"10.20944\/preprints201802.0077.v1"},{"key":"ref_142","doi-asserted-by":"crossref","first-page":"1","DOI":"10.2217\/14796708.3.1.1","article-title":"The nose may help the brain: Intranasal drug delivery for treating neurological diseases","volume":"3","author":"Ying","year":"2008","journal-title":"Future Neurol."},{"key":"ref_143","doi-asserted-by":"crossref","first-page":"4169","DOI":"10.1016\/j.actbio.2011.07.025","article-title":"Development and evaluation of olanzapine-loaded PLGA nanoparticles for nose-to-brain delivery: In vitro and in vivo studies","volume":"7","author":"Seju","year":"2011","journal-title":"Acta Biomater."},{"key":"ref_144","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1016\/j.ijpharm.2004.01.039","article-title":"Preparation of nimodipine-loaded microemulsion for intranasal delivery and evaluation on the targeting efficiency to the brain","volume":"275","author":"Zhang","year":"2004","journal-title":"Int. J. Pharm."},{"key":"ref_145","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1016\/j.jconrel.2014.06.053","article-title":"Quantitative analysis of drug delivery to the brain via nasal route","volume":"189","author":"Kozlovskaya","year":"2014","journal-title":"J. Control. Release"},{"key":"ref_146","doi-asserted-by":"crossref","first-page":"367","DOI":"10.1016\/j.drudis.2011.10.028","article-title":"Is there a clinical future for polymeric nanoparticles as brain-targeting drug delivery agents?","volume":"17","author":"Costantino","year":"2012","journal-title":"Drug Discov. 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