{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,27]],"date-time":"2026-10-27T16:29:23Z","timestamp":1793118563460,"version":"4.5.0"},"reference-count":115,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2018,2,1]],"date-time":"2018-02-01T00:00:00Z","timestamp":1517443200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"}],"content-domain":{"domain":["elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Life Sciences"],"published-print":{"date-parts":[[2018,2]]},"DOI":"10.1016\/j.lfs.2017.12.025","type":"journal-article","created":{"date-parts":[[2017,12,22]],"date-time":"2017-12-22T03:07:41Z","timestamp":1513912061000},"page":"44-52","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":682,"special_numbering":"C","title":["Mechanism of intranasal drug delivery directly to the brain"],"prefix":"10.1016","volume":"195","author":[{"given":"Tyler P.","family":"Crowe","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M. Heather West","family":"Greenlee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anumantha G.","family":"Kanthasamy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Walter H.","family":"Hsu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.lfs.2017.12.025_bb0005","doi-asserted-by":"crossref","first-page":"1250","DOI":"10.1289\/ehp.7567","article-title":"Neurodegenerative diseases: an overview of environmental risk factors","volume":"113","author":"Brown","year":"2005","journal-title":"Environ. Health Perspect."},{"key":"10.1016\/j.lfs.2017.12.025_bb0010","doi-asserted-by":"crossref","first-page":"1778","DOI":"10.1212\/WNL.0b013e31828726f5","article-title":"Alzheimer disease in the United States (2010\u20132050) estimated using the 2010 census","volume":"80","author":"Herbert","year":"2013","journal-title":"Neurology"},{"key":"10.1016\/j.lfs.2017.12.025_bb0015","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1002\/j.1875-9114.1998.tb03880.x","article-title":"Economic considerations in Alzheimer's disease","volume":"18","author":"Meek","year":"1998","journal-title":"Pharmacotherapy"},{"key":"10.1016\/j.lfs.2017.12.025_bb0020","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1083\/jcb.34.1.207","article-title":"Fine structural localization of a blood-brain barrier to exogenous peroxidase","volume":"34","author":"Reese","year":"1967","journal-title":"J. Cell Biol."},{"key":"10.1016\/j.lfs.2017.12.025_bb0025","doi-asserted-by":"crossref","first-page":"S3","DOI":"10.1186\/1471-2377-9-S1-S3","article-title":"Characteristics of compounds that cross the blood-brain barrier","volume":"9","author":"Banks","year":"2009","journal-title":"BMC Neurol."},{"key":"10.1016\/j.lfs.2017.12.025_bb0030","series-title":"Drug Transporters: Molecular Characterization and Role in Drug Disposition","article-title":"Drug transport in the brain","author":"Ronaldson","year":"2006"},{"key":"10.1016\/j.lfs.2017.12.025_bb0035","doi-asserted-by":"crossref","first-page":"3","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":"10.1016\/j.lfs.2017.12.025_bb0040","first-page":"465","article-title":"Die arachnoidalraum, ein lymphraum und sein zusammenhang mit den perichorioidalraum","volume":"7","author":"Schwalbe","year":"1869","journal-title":"Zentralbl. Med. Wiss."},{"key":"10.1016\/j.lfs.2017.12.025_bb0045","doi-asserted-by":"crossref","first-page":"260","DOI":"10.1002\/cne.902510209","article-title":"Avenues for entry of peripherally administered protein to the CNS in mouse, rat, and squirrel monkey","volume":"251","author":"Balin","year":"1986","journal-title":"J. Comp. Neurol."},{"key":"10.1016\/j.lfs.2017.12.025_bb0050","series-title":"Neurologic Agents for Nasal Administration to the Brain","author":"Frey","year":"1991"},{"key":"10.1016\/j.lfs.2017.12.025_bb0055","unstructured":"Frey WH II. Method of Administering Neurologic Agents to the Brain. US Patent 6,180,603 B1, January 8, 1997."},{"key":"10.1016\/j.lfs.2017.12.025_bb0060","unstructured":"Frey WH II. Method for Administering Insulin to the Brain. US Patent 6,313,093 B1, November 6, 2001."},{"key":"10.1016\/j.lfs.2017.12.025_bb0065","doi-asserted-by":"crossref","first-page":"451","DOI":"10.1016\/j.neurobiolaging.2005.03.016","article-title":"Effects of intranasal insulin on cognition in memory-impaired older adults: modulation by APOE genotype","volume":"27","author":"Reger","year":"2006","journal-title":"Neurobiol. Aging"},{"key":"10.1016\/j.lfs.2017.12.025_bb0070","doi-asserted-by":"crossref","first-page":"323","DOI":"10.3233\/JAD-2008-13309","article-title":"Intranasal insulin administration dose-dependently modulates verbal memory and plasma amyloid-beta in memory-impaired older adults","volume":"13","author":"Reger","year":"2008","journal-title":"J. Alzheimers Dis."},{"key":"10.1016\/j.lfs.2017.12.025_bb0075","doi-asserted-by":"crossref","first-page":"63","DOI":"10.3233\/JAD-2005-7107","article-title":"Impaired insulin and insulin-like growth factor expression and signaling mechanisms in Alzheimer's disease\u2014is this type 3 diabetes?","volume":"7","author":"Steen","year":"2005","journal-title":"J. Alzheimers Dis."},{"key":"10.1016\/j.lfs.2017.12.025_bb0080","doi-asserted-by":"crossref","first-page":"2088","DOI":"10.1210\/en.2005-1016","article-title":"Brain uptake of intranasally applied radioiodinated leptin in Wistar rats","volume":"147","author":"Fliedner","year":"2006","journal-title":"Endocrinology"},{"key":"10.1016\/j.lfs.2017.12.025_bb0085","doi-asserted-by":"crossref","first-page":"E10","DOI":"10.1152\/ajpendo.00468.2002","volume":"285","author":"Banks","year":"2003","journal-title":"Am. J. Phys. Endocrinol. Metab."},{"issue":"145","key":"10.1016\/j.lfs.2017.12.025_bb0090","doi-asserted-by":"crossref","first-page":"2696","DOI":"10.1210\/en.2003-1431","article-title":"Central nervous and metabolic effects of intranasally applied leptin","volume":"204","author":"Schulz","year":"2004","journal-title":"Endocrinology"},{"key":"10.1016\/j.lfs.2017.12.025_bb0095","doi-asserted-by":"crossref","first-page":"479","DOI":"10.1002\/ddr.21343","article-title":"Effects of intranasal oxytocin on long-term memory in healthy humans: a systemic review","volume":"77","author":"Brambilla","year":"2016","journal-title":"Drug Dev. Res."},{"key":"10.1016\/j.lfs.2017.12.025_bb0100","doi-asserted-by":"crossref","first-page":"569","DOI":"10.1016\/j.neuroscience.2015.07.016","article-title":"Intranasal administration of glial-derived neurotrophic factor (GDNF) rapidly and significantly increases whole-brain GDNF level in rats","volume":"303","author":"Bender","year":"2015","journal-title":"Neuroscience"},{"key":"10.1016\/j.lfs.2017.12.025_bb0105","doi-asserted-by":"crossref","first-page":"338","DOI":"10.3109\/10717544.2011.557785","article-title":"Intranasal nerve growth factor enhances striatal neurogenesis in adult rats with focal cerebral ischemia","volume":"18","author":"Zhu","year":"2011","journal-title":"Drug Deliv."},{"key":"10.1016\/j.lfs.2017.12.025_bb0110","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1124\/jpet.114.216705","article-title":"Intranasal administration as a route for drug delivery to the brain: evidence for a unique pathway for albumin","volume":"351","author":"Falcone","year":"2014","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"10.1016\/j.lfs.2017.12.025_bb0115","first-page":"264","article-title":"Absence of albumin receptor on brain capillaries in vivo or in vitro","volume":"249","author":"Pardridge","year":"1985","journal-title":"Am. J. Phys."},{"key":"10.1016\/j.lfs.2017.12.025_bb0120","first-page":"285","article-title":"Gene knockout in the olfactory bulb, amygdala, and hypothalamus by intranasal siRNA administration","volume":"42","author":"Kim","year":"2009","journal-title":"Kor. J. Anat."},{"key":"10.1016\/j.lfs.2017.12.025_bb0125","doi-asserted-by":"crossref","first-page":"315","DOI":"10.1016\/j.ejcb.2009.02.001","article-title":"Intranasal delivery of cells to the brain","volume":"88","author":"Danielyan","year":"2009","journal-title":"Eur. J. Cell Biol."},{"key":"10.1016\/j.lfs.2017.12.025_bb0130","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1016\/j.neulet.2012.02.037","article-title":"Intranasal delivery of siRNA to the olfactory bulbs of mice via the olfactory nerve pathway","volume":"513","author":"Renner","year":"2012","journal-title":"Neurosci. Lett."},{"key":"10.1016\/j.lfs.2017.12.025_bb0135","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1007\/BF02991098","article-title":"Anatomy and physiology of the nose\u2014pathophysiologic alteration in allergic rhinitis","volume":"2","author":"Mygind","year":"1984","journal-title":"Clin. Rev. Allergy"},{"key":"10.1016\/j.lfs.2017.12.025_bb0140","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1016\/S0169-409X(97)00058-6","article-title":"Anatomy, physiology and function of the nasal cavities in health and disease","volume":"29","author":"Mygind","year":"1998","journal-title":"Adv. Drug Deliv. Rev."},{"key":"10.1016\/j.lfs.2017.12.025_bb0145","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1111\/j.1398-9995.1999.tb04402.x","article-title":"Applied anatomy and physiology of the nose and paranasal sinuses","volume":"57","author":"Watelet","year":"1999","journal-title":"Allergy"},{"key":"10.1016\/j.lfs.2017.12.025_bb0150","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1016\/S0169-409X(97)00059-8","article-title":"Nasal mucociliary clearance as a factor in nasal drug delivery","volume":"29","author":"Merkus","year":"1998","journal-title":"Adv. Drug Deliv. Rev."},{"key":"10.1016\/j.lfs.2017.12.025_bb0155","doi-asserted-by":"crossref","first-page":"967","DOI":"10.1016\/S1359-6446(02)02452-2","article-title":"Permeability issues in nasal drug delivery","volume":"7","author":"Arora","year":"2002","journal-title":"Drug Discov. Today"},{"key":"10.1016\/j.lfs.2017.12.025_bb0160","doi-asserted-by":"crossref","first-page":"165","DOI":"10.2174\/1567201053586047","article-title":"Intranasal drug delivery for brain targeting","volume":"2","author":"Vyas","year":"2005","journal-title":"Curr. Drug Deliv."},{"key":"10.1016\/j.lfs.2017.12.025_bb0165","doi-asserted-by":"crossref","first-page":"288","DOI":"10.18433\/J3NC79","article-title":"Intranasal drug delivery: how, why and what for?","volume":"12","author":"Pires","year":"2009","journal-title":"J. Pharm. Pharm. Sci."},{"key":"10.1016\/j.lfs.2017.12.025_bb0170","doi-asserted-by":"crossref","first-page":"317","DOI":"10.1023\/B:NEUR.0000010089.37032.48","article-title":"Ensheathment of the olfactory nerves in adult rat","volume":"32","author":"Field","year":"2003","journal-title":"J. Neurocytol."},{"key":"10.1016\/j.lfs.2017.12.025_bb0175","doi-asserted-by":"crossref","first-page":"403","DOI":"10.1002\/cne.903460306","article-title":"Central olfactory connections in the macaque monkey","volume":"346","author":"Carmichael","year":"1994","journal-title":"J. Comp. Neurol."},{"key":"10.1016\/j.lfs.2017.12.025_bb0180","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1002\/glia.20241","article-title":"Olfactory ensheathing cells and olfactory nerve fibroblasts maintain continuous open channels for regrowth of olfactory nerve fibres","volume":"52","author":"Li","year":"2005","journal-title":"Glia"},{"key":"10.1016\/j.lfs.2017.12.025_bb0185","doi-asserted-by":"crossref","first-page":"419","DOI":"10.1093\/infdis\/jiu097","article-title":"Evidence for influenza virus CNS invasion along the olfactory route in an immunocompromised infant","volume":"210","author":"van Riel","year":"2014","journal-title":"J. Infect. Dis."},{"key":"10.1016\/j.lfs.2017.12.025_bb0190","doi-asserted-by":"crossref","first-page":"1028","DOI":"10.1016\/S0140-6736(87)92288-4","article-title":"Uptake of aluminium into central nervous system along nasal olfactory pathways","volume":"1","author":"Perl","year":"1987","journal-title":"Lancet"},{"key":"10.1016\/j.lfs.2017.12.025_bb0195","series-title":"Ciba Foundation Symposium - Taste and Smell in Vertebrates","article-title":"The olfactory neuron and the blood-brain barrier","author":"de Lorenzo","year":"1970"},{"key":"10.1016\/j.lfs.2017.12.025_bb0200","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1007\/BF00688493","article-title":"Uptake of exogenous proteins in mouse olfactory cells","volume":"19","author":"Kristenssen","year":"1971","journal-title":"Acta Neuropathol."},{"key":"10.1016\/j.lfs.2017.12.025_bb0205","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1016\/0006-8993(92)91338-F","article-title":"Olfactory bulb transplantation into the olfactory bulb of neonatal rats: a WGA-HRP study","volume":"588","author":"Zigova","year":"1992","journal-title":"Brain Res."},{"key":"10.1016\/j.lfs.2017.12.025_bb0210","doi-asserted-by":"crossref","first-page":"632","DOI":"10.1002\/cne.902420410","article-title":"Endocytic and exocytic pathways of the neuronal secretory process and trans-synaptic transfer of wheat germ agglutinin-horseradish peroxidase in vivo","volume":"242","author":"Broadwell","year":"1985","journal-title":"J. Comp. Neurol."},{"key":"10.1016\/j.lfs.2017.12.025_bb0215","doi-asserted-by":"crossref","first-page":"278","DOI":"10.1016\/0006-8993(95)00637-6","article-title":"Quantitative analysis of the olfactory pathway for drug delivery to the brain","volume":"692","author":"Thorne","year":"1995","journal-title":"Brain Res."},{"key":"10.1016\/j.lfs.2017.12.025_bb0220","doi-asserted-by":"crossref","first-page":"617","DOI":"10.1016\/0306-4522(91)90354-Q","article-title":"Central projections of trigeminal primary afferents innervating the nasal mucosa: a horseradish peroxidase study in the rat","volume":"41","author":"Anton","year":"1991","journal-title":"Neuroscience"},{"key":"10.1016\/j.lfs.2017.12.025_bb0225","doi-asserted-by":"crossref","first-page":"895","DOI":"10.1016\/0306-4522(85)90152-6","article-title":"A comparison between wheat germ agglutinin-and choleragenoid-horseradish peroxidase as anterogradely transported markers in central branches of primary sensory neurons in the rat with some observations in the cat","volume":"14","author":"Robertson","year":"1985","journal-title":"Neuroscience"},{"key":"10.1016\/j.lfs.2017.12.025_bb0230","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1111\/j.1365-2990.1990.tb01158.x","article-title":"Human herpes virus infections and Alzheimer's disease","volume":"16","author":"Dealtly","year":"1990","journal-title":"Neuropathol. Appl. Neurobiol."},{"key":"10.1016\/j.lfs.2017.12.025_bb0235","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1016\/j.jalz.2012.07.005","article-title":"Intracerebral propagation of Alzheimer's disease: strengthening evidence of a herpes simplex virus etiology","volume":"9","author":"Ball","year":"2013","journal-title":"Alzheimers Dement."},{"key":"10.1016\/j.lfs.2017.12.025_bb0240","doi-asserted-by":"crossref","first-page":"180","DOI":"10.1001\/archotol.1979.00790160014003","article-title":"Subarachnoid space of the CNS, nasal mucosa, and lymphatic system","volume":"105","author":"Jackson","year":"1979","journal-title":"Arch. Otolaryngol."},{"key":"10.1016\/j.lfs.2017.12.025_bb0245","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1016\/0361-9230(85)90129-7","article-title":"Transport of molecules from nose to brain: transneuronal anterograde and retrograde labeling in the rat olfactory system by wheat germ agglutinin-horseradish peroxidase applied to the nasal epithelium","volume":"15","author":"Shipley","year":"1985","journal-title":"Brain Res. Bull."},{"key":"10.1016\/j.lfs.2017.12.025_bb0250","doi-asserted-by":"crossref","first-page":"697","DOI":"10.1016\/0306-4522(87)90366-6","article-title":"A quantitative study of anterograde and retrograde axonal transport of exogenous proteins in olfactory nerve C-fibers","volume":"22","author":"Buchner","year":"1987","journal-title":"Neuroscience"},{"key":"10.1016\/j.lfs.2017.12.025_bb0255","doi-asserted-by":"crossref","first-page":"443","DOI":"10.1016\/0006-8993(80)91293-7","article-title":"Axonal transport of substance P in the vagus and sciatic nerves of the guinea pig","volume":"191","author":"Brimijoin","year":"1980","journal-title":"Brain Res."},{"key":"10.1016\/j.lfs.2017.12.025_bb0260","doi-asserted-by":"crossref","first-page":"614","DOI":"10.1016\/j.addr.2011.11.002","article-title":"Intranasal delivery of biologics to central nervous system","volume":"64","author":"Lochhead","year":"2012","journal-title":"Adv. Drug Deliv. Rev."},{"key":"10.1016\/j.lfs.2017.12.025_bb0265","first-page":"237","article-title":"Axonal and transneuronal transport of wheat germ agglutinin demonstrated by immunocytochemistry","volume":"28","author":"Ruda","year":"1982","journal-title":"Neurosci. Lett."},{"key":"10.1016\/j.lfs.2017.12.025_bb0270","doi-asserted-by":"crossref","first-page":"347","DOI":"10.1242\/jcs.9.2.347","article-title":"The neuropil of the glomeruli of the olfactory bulb","volume":"9","author":"Pinching","year":"1971","journal-title":"J. Cell Sci."},{"key":"10.1016\/j.lfs.2017.12.025_bb0275","doi-asserted-by":"crossref","first-page":"120","DOI":"10.3389\/fncir.2010.00120","article-title":"Differential axonal projection of mitral and tufted cells in the mouse main olfactory system","volume":"4","author":"Nagayama","year":"2010","journal-title":"Front. Neural. Circuits"},{"key":"10.1016\/j.lfs.2017.12.025_bb0280","doi-asserted-by":"crossref","first-page":"152","DOI":"10.1016\/0006-8993(77)90978-7","article-title":"The axonal projection patterns of the mitral and tufted cells of the olfactory bulb in the rat","volume":"129","author":"Haberly","year":"1977","journal-title":"Brain Res."},{"key":"10.1016\/j.lfs.2017.12.025_bb0285","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1007\/978-1-4684-3264-0_4","article-title":"The morphological approach to the study of normal and abnormal brain permeability","volume":"69","author":"Brightman","year":"1976","journal-title":"Adv. Exp. Med. Biol."},{"key":"10.1016\/j.lfs.2017.12.025_bb0290","doi-asserted-by":"crossref","first-page":"588","DOI":"10.1016\/j.bbamem.2007.08.017","article-title":"Transmembrane proteins of tight junctions","volume":"1778","author":"Chiba","year":"2008","journal-title":"Biochim. Biophys. Acta"},{"key":"10.1016\/j.lfs.2017.12.025_bb0295","doi-asserted-by":"crossref","first-page":"1029","DOI":"10.1023\/A:1015802427428","article-title":"The transport barrier of epithelia: a comparative study on membrane permeability and charge selectivity in the rabbit","volume":"9","author":"Rojanasakul","year":"1992","journal-title":"Pharm. Res."},{"key":"10.1016\/j.lfs.2017.12.025_bb0300","doi-asserted-by":"crossref","first-page":"346","DOI":"10.1016\/S1461-5347(00)00302-3","article-title":"Enhancing paracellular permeability by modulating epithelial tight junctions","volume":"3","author":"Ward","year":"2000","journal-title":"Pharm. Sci. Technol. Today"},{"key":"10.1016\/j.lfs.2017.12.025_bb0305","doi-asserted-by":"crossref","first-page":"362","DOI":"10.1016\/0166-2236(90)90017-5","article-title":"Olfactory neurogenesis: genetic or environmental controls?","volume":"13","author":"Farbman","year":"1990","journal-title":"Trends Neurosci."},{"key":"10.1016\/j.lfs.2017.12.025_bb0310","doi-asserted-by":"crossref","first-page":"204","DOI":"10.1002\/jemt.10150","article-title":"Apoptosis in the mature and developing olfactory neuroepithelium","volume":"58","author":"Cowan","year":"2002","journal-title":"Microsc. Res. Tech."},{"key":"10.1016\/j.lfs.2017.12.025_bb0315","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1007\/BF00221071","article-title":"Freeze-fracture and tracer experiments on the permeability of the zonulae occludentes in the olfactory mucosa of vertebrates","volume":"154","author":"Altner","year":"1974","journal-title":"Cell Tissue Res."},{"key":"10.1016\/j.lfs.2017.12.025_bb0320","series-title":"Handbook of Olfaction and Gustation","article-title":"Neurogenesis in the adult olfactory neuroepithelium","author":"Mackay-Sim","year":"2003"},{"key":"10.1016\/j.lfs.2017.12.025_bb0325","doi-asserted-by":"crossref","first-page":"1927","DOI":"10.1002\/jps.1143","article-title":"Gastrointestinal persorption and tissue distribution of differently sized colloidal gold nanoparticles","volume":"90","author":"Hillyet","year":"2001","journal-title":"J. Pharm. Sci."},{"key":"10.1016\/j.lfs.2017.12.025_bb0330","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1016\/j.neuroscience.2016.01.020","article-title":"Intranasal insulin protects against substantia nigra dopaminergic neuronal loss and alleviates motor deficits induced by 6-OHDA in rats","volume":"318","author":"Pang","year":"2016","journal-title":"Neuroscience"},{"key":"10.1016\/j.lfs.2017.12.025_bb0335","doi-asserted-by":"crossref","first-page":"361","DOI":"10.1016\/j.expneurol.2009.03.021","article-title":"Intranasal administration of IGF-1 attenuates hypoxic-ischemia brain injury in neonatal rats","volume":"217","author":"Lin","year":"2009","journal-title":"Exp. Neurol."},{"key":"10.1016\/j.lfs.2017.12.025_bb0340","doi-asserted-by":"crossref","DOI":"10.4172\/2155-9899.1000142","article-title":"Intranasal delivery of neural stem cells: a CNS-specific, non-invasive cell-based therapy for experimental autoimmune encephalomyelitis","volume":"4","author":"Wu","year":"2013","journal-title":"J. Clin. Cell Immunol."},{"key":"10.1016\/j.lfs.2017.12.025_bb0345","doi-asserted-by":"crossref","first-page":"866","DOI":"10.5966\/sctm.2012-0045","article-title":"Intranasal delivery of neural stem\/progenitor cells: a noninvasive passage to target intracerebral glioma","volume":"1","author":"Reitz","year":"2012","journal-title":"Stem Cells Transl. Med."},{"key":"10.1016\/j.lfs.2017.12.025_bb0350","doi-asserted-by":"crossref","first-page":"140","DOI":"10.1038\/mt.2013.199","article-title":"Intranasal delivery of mesenchymal stem cells significantly extends survival of irradiated mice with experimental brain tumors","volume":"22","author":"Balyasnikova","year":"2014","journal-title":"Mol. Ther."},{"key":"10.1016\/j.lfs.2017.12.025_bb0355","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1089\/rej.2010.1130","article-title":"Therapeutic efficacy of intranasally delivered mesenchymal stem cells in a rat model of Parkinson disease","volume":"14","author":"Danielyan","year":"2011","journal-title":"Rejuvenation Res."},{"key":"10.1016\/j.lfs.2017.12.025_bb0360","first-page":"419","article-title":"Nasal administration of stem cells: a promising novel route to treat neonatal ischemic brain damage","volume":"68","author":"van Velthoven","year":"2010","journal-title":"Pediatr. Res."},{"key":"10.1016\/j.lfs.2017.12.025_bb0365","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0051253","article-title":"Intranasal mesenchymal stem cell treatment for neonatal brain damage: long-term cognitive and sensorimotor improvement","volume":"8","author":"Donega","year":"2013","journal-title":"PLoS One"},{"key":"10.1016\/j.lfs.2017.12.025_bb0370","doi-asserted-by":"crossref","first-page":"977","DOI":"10.3727\/096368912X657251","article-title":"Delayed intranasal delivery of hypoxic-preconditioned bone marrow mesenchymal stem cells enhanced cell homing and therapeutic benefits after ischemic stroke in mice","volume":"22","author":"Wei","year":"2013","journal-title":"Cell Transplant."},{"issue":"9","key":"10.1016\/j.lfs.2017.12.025_bb0375","first-page":"112","article-title":"CAR\/FoxP3-engineered T regulatory cells target the CNS and suppress EAE upon intranasal delivery","volume":"30","author":"Fransson","year":"2012","journal-title":"J. Neuroinflammation"},{"key":"10.1016\/j.lfs.2017.12.025_bb0380","doi-asserted-by":"crossref","first-page":"111","DOI":"10.3171\/2014.10.SPINE14690","article-title":"Intranasal delivery of bone marrow stromal cells to spinal cord lesions","volume":"23","author":"Ninomiya","year":"2015","journal-title":"J. Neurosurg. Spine"},{"key":"10.1016\/j.lfs.2017.12.025_bb0385","doi-asserted-by":"crossref","first-page":"892","DOI":"10.1016\/j.bbamem.2008.09.016","article-title":"Potential use of tight junction modulators to reversibly open membranous barriers and improve drug delivery","volume":"1788","author":"Deli","year":"2009","journal-title":"Biochim. Biophys. Acta Biomembr."},{"key":"10.1016\/j.lfs.2017.12.025_bb0390","doi-asserted-by":"crossref","first-page":"1838","DOI":"10.1023\/B:PHAM.0000003383.86238.d1","article-title":"Poly-L-arginine enhances paracellular permeability via serine\/threonine phosphorylation of ZO-1 and tyrosine dephosphorylation of occludin in rabbit nasal epithelium","volume":"20","author":"Ohtake","year":"2003","journal-title":"Pharm. Res."},{"key":"10.1016\/j.lfs.2017.12.025_bb0395","doi-asserted-by":"crossref","first-page":"432","DOI":"10.1124\/mol.107.043711","article-title":"Protein kinase C enhances tight junction barrier function of human nasal epithelial cells in primary culture by transcriptional regulation","volume":"74","author":"Koizumi","year":"2008","journal-title":"Mol. Pharmacol."},{"key":"10.1016\/j.lfs.2017.12.025_bb0400","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1023\/A:1022485816755","article-title":"Poly-L-arginine predominantly increases the paracellular permeability of hydrophilic macromolecules across rabbit nasal epithelium in vitro","volume":"20","author":"Ohtake","year":"2003","journal-title":"Pharm. Res."},{"key":"10.1016\/j.lfs.2017.12.025_bb0405","doi-asserted-by":"crossref","first-page":"8","DOI":"10.3109\/10717544.2013.840017","article-title":"Manipulation of olfactory tight junctions using papaverine to enhance intranasal delivery of gemcitabine to the brain","volume":"21","author":"Krishan","year":"2014","journal-title":"Drug Deliv"},{"key":"10.1016\/j.lfs.2017.12.025_bb0410","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1016\/S0378-5173(99)00451-2","article-title":"Chitaosans as nasal absorption enhancers of peptides: comparison between free amine chitosans and soluble salts","volume":"197","author":"Tengamnuay","year":"2000","journal-title":"Int. J. Pharm."},{"key":"10.1016\/j.lfs.2017.12.025_bb0415","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1023\/B:PHAM.0000012150.60180.e3","article-title":"Effect of chitosan on epithelial cell tight junctions","volume":"21","author":"Smith","year":"2004","journal-title":"Pharm. Res."},{"key":"10.1016\/j.lfs.2017.12.025_bb0420","doi-asserted-by":"crossref","first-page":"304","DOI":"10.1016\/j.colsurfb.2015.06.054","article-title":"Chitosan coated nanostructured lipid carriers for brain delivery of proteins by intranasal administration","volume":"134","author":"Gartziandia","year":"2015","journal-title":"Colloids Surf. B: Biointerfaces"},{"key":"10.1016\/j.lfs.2017.12.025_bb0425","doi-asserted-by":"crossref","first-page":"442","DOI":"10.1016\/j.ijpharm.2014.07.025","article-title":"Effect of surface charge on the brain delivery of nanostructured lipid carriers in situ gels via the nasal route","volume":"473","author":"Gabel","year":"2014","journal-title":"Int. J. Pharm."},{"key":"10.1016\/j.lfs.2017.12.025_bb0430","doi-asserted-by":"crossref","first-page":"1652","DOI":"10.1002\/jps.21043","article-title":"Polymeric enhancers of mucosal epithelia permeability: synthesis, transepithelial penetration-enhancing properties, mechanism of action, safety issues","volume":"97","author":"Di Colo","year":"2008","journal-title":"J. Pharm. Sci."},{"key":"10.1016\/j.lfs.2017.12.025_bb0435","doi-asserted-by":"crossref","first-page":"158","DOI":"10.1016\/j.addr.2008.11.002","article-title":"Mucus-penetrating nanoparticles for drug and gene delivery to mucosal tissues","volume":"61","author":"Lai","year":"2009","journal-title":"Adv. Drug Deliv. Rev."},{"key":"10.1016\/j.lfs.2017.12.025_bb0440","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1002\/aja.1000620106","article-title":"The nasal mucosa and the subarachnoid space","volume":"62","author":"Faber","year":"1937","journal-title":"Am. J. Anat."},{"key":"10.1016\/j.lfs.2017.12.025_bb0445","doi-asserted-by":"crossref","first-page":"505","DOI":"10.1007\/s40263-013-0076-8","article-title":"Intranasal insulin as a treatment for Alzheimer's disease: a review of basic research and clinical evidence","volume":"27","author":"Freiherr","year":"2013","journal-title":"CNS Drugs"},{"key":"10.1016\/j.lfs.2017.12.025_bb0450","doi-asserted-by":"crossref","first-page":"1159","DOI":"10.1002\/ca.22415","article-title":"Arterial supply of the upper cranial nerves: a comprehensive review","volume":"27","author":"Hendrix","year":"2014","journal-title":"Clin. Anat."},{"key":"10.1016\/j.lfs.2017.12.025_bb0455","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1080\/10255840310001606116","article-title":"Arterial pulsation-driven cerebrospinal fluid flow in the perivascular space: a computational mode","volume":"6","author":"Bilston","year":"2003","journal-title":"Comput. Methods Biomech. Biomed. Eng."},{"key":"10.1016\/j.lfs.2017.12.025_bb0460","doi-asserted-by":"crossref","first-page":"686","DOI":"10.3171\/jns.1997.86.4.0686","article-title":"Arterial pulsation-dependent perivascular cerebrospinal fluid flow into the central canal in the sheep spinal cord","volume":"86","author":"Stoodley","year":"1997","journal-title":"J. Neurosurg."},{"key":"10.1016\/j.lfs.2017.12.025_bb0465","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1016\/0006-8993(91)91275-6","article-title":"Distribution of extracellular tracers in perivascular spaces of the rat brain","volume":"545","author":"Ichimura","year":"1991","journal-title":"Brain Res."},{"key":"10.1016\/j.lfs.2017.12.025_bb0470","doi-asserted-by":"crossref","first-page":"629","DOI":"10.1084\/jem.68.4.629","article-title":"The lymphatic pathway from the nose and pharynx: the absorption of dyes","volume":"68","author":"Yoffey","year":"1938","journal-title":"J. Exp. Med."},{"key":"10.1016\/j.lfs.2017.12.025_bb0475","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1089\/lrb.2004.2.139","article-title":"Lymphatic vessels gain access to cerebrospinal fluid through unique association with olfactory nerves","volume":"2","author":"Zakharov","year":"2004","journal-title":"Lymphat. Res. Biol."},{"key":"10.1016\/j.lfs.2017.12.025_bb0480","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1186\/1743-8454-1-2","article-title":"Evidence of connections between cerebrospinal fluid and nasal lymphatic vessels in humans, non-human primates and other mammalian species","volume":"1","author":"Johnston","year":"2004","journal-title":"Cerebrospinal Fluid Res."},{"key":"10.1016\/j.lfs.2017.12.025_bb0485","doi-asserted-by":"crossref","first-page":"535","DOI":"10.1002\/jps.2600760709","article-title":"Analysis of structural requirements for the absorption of drugs and macromolecules from the nasal cavity","volume":"76","author":"McMartin","year":"1987","journal-title":"J. Pharm. Sci."},{"key":"10.1016\/j.lfs.2017.12.025_bb0490","doi-asserted-by":"crossref","first-page":"481","DOI":"10.1016\/j.neuroscience.2004.05.029","article-title":"Delivery of insulin-like growth factor-I to the rat brain and spinal cord along olfactory and trigeminal pathways following intranasal administration","volume":"127","author":"Thorne","year":"2004","journal-title":"Neuroscience"},{"key":"10.1016\/j.lfs.2017.12.025_bb0495","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1016\/j.ymthe.2006.02.018","article-title":"The \u201cperivascular pump\u201d driven by arterial pulsation is a powerful mechanism for the distribution of therapeutic molecules within the brain","volume":"14","author":"Hadaczek","year":"2006","journal-title":"Mol. Ther."},{"key":"10.1016\/j.lfs.2017.12.025_bb0500","doi-asserted-by":"crossref","first-page":"371","DOI":"10.1038\/jcbfm.2014.215","article-title":"Rapid transport within cerebral perivascular spaces underlies widespread tracer distribution in the brain after intranasal administration","volume":"35","author":"Lochhead","year":"2015","journal-title":"J. Cereb. Blood Flow Metab."},{"key":"10.1016\/j.lfs.2017.12.025_bb0505","doi-asserted-by":"crossref","first-page":"1534","DOI":"10.1038\/cr.2011.83","article-title":"Identification and characterization of neuroblasts in the subventricular zone and rostral migratory stream of the adult human brain","volume":"21","author":"Wang","year":"2011","journal-title":"Cell Res."},{"key":"10.1016\/j.lfs.2017.12.025_bb0510","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0018711","article-title":"The rostal migratory stream plays a key role in intranasal delivery of drugs to the CNS","volume":"6","author":"Scranton","year":"2011","journal-title":"PLoS One"},{"key":"10.1016\/j.lfs.2017.12.025_bb0515","doi-asserted-by":"crossref","first-page":"715","DOI":"10.3233\/JAD-150307","article-title":"Central nervous system delivery of intranasal insulin: mechanisms of uptake and effects on cognition","volume":"47","author":"Salameh","year":"2015","journal-title":"J. Alzheimers Dis."},{"key":"10.1016\/j.lfs.2017.12.025_bb0520","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1007\/s10571-009-9463-6","article-title":"Intranasal delivery of human beta-amyloid peptide in rats: effective brain targeting","volume":"30","author":"Sipos","year":"2010","journal-title":"Cell. Mol. Neurobiol."},{"key":"10.1016\/j.lfs.2017.12.025_bb0525","doi-asserted-by":"crossref","first-page":"1326","DOI":"10.1016\/j.psyneuen.2004.04.003","article-title":"Intranasal insulin improves memory in humans","volume":"29","author":"Benedict","year":"2004","journal-title":"Psychoneuroendocrinology"},{"key":"10.1016\/j.lfs.2017.12.025_bb0530","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1038\/sj.npp.1301193","article-title":"Intranasal insulin improves memory in humans: superiority of insulin aspart","volume":"32","author":"Benedict","year":"2007","journal-title":"Neuropsychopharmacology"},{"key":"10.1016\/j.lfs.2017.12.025_bb0535","doi-asserted-by":"crossref","first-page":"751","DOI":"10.2337\/dc13-1672","article-title":"Enhancement of vasoreactivity and cognition by intranasal insulin in type 2 diabetes","volume":"37","author":"Novak","year":"2014","journal-title":"Diabetes Care"},{"key":"10.1016\/j.lfs.2017.12.025_bb0540","doi-asserted-by":"crossref","first-page":"1339","DOI":"10.1210\/jc.2007-2606","article-title":"Differential sensitivity of men and women to anorexigenic and memory-improving effects of intranasal insulin","volume":"93","author":"Benedict","year":"2008","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"10.1016\/j.lfs.2017.12.025_bb0545","doi-asserted-by":"crossref","first-page":"E468","DOI":"10.1210\/jc.2010-0744","article-title":"Comparable sensitivity of postmenopausal and young women to the effects of intranasal insulin on food intake and working memory","volume":"95","author":"Krug","year":"2010","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"10.1016\/j.lfs.2017.12.025_bb0550","doi-asserted-by":"crossref","first-page":"440","DOI":"10.1212\/01.WNL.0000265401.62434.36","article-title":"Intranasal insulin improves cognition and modulates beta-amyloid in early AD","volume":"70","author":"Reger","year":"2008","journal-title":"Neurology"},{"key":"10.1016\/j.lfs.2017.12.025_bb0555","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1001\/archneurol.2011.233","article-title":"Intranasal insulin therapy for Alzheimer disease and amnestic mild cognitive impairment: a pilot clinical trial","volume":"69","author":"Craft","year":"2012","journal-title":"Arch. Neurol."},{"key":"10.1016\/j.lfs.2017.12.025_bb0560","doi-asserted-by":"crossref","first-page":"897","DOI":"10.3233\/JAD-141791","article-title":"Long-acting intranasal insulin detemir improves cognition for adults with mild cognitive impairment or early-stage Alzheimer's disease dementia","volume":"44","author":"Claxton","year":"2015","journal-title":"J. Alzheimers Dis."},{"key":"10.1016\/j.lfs.2017.12.025_bb0565","doi-asserted-by":"crossref","first-page":"514","DOI":"10.1038\/nn0602-849","article-title":"Sniffing neuropeptides: a transnasal approach to the human brain","volume":"5","author":"Born","year":"2002","journal-title":"Nat. Neurosci."},{"key":"10.1016\/j.lfs.2017.12.025_bb0570","doi-asserted-by":"crossref","first-page":"1185","DOI":"10.1007\/s40263-014-0214-y","article-title":"A single-dose pilot trial of intranasal rapid-acting insulin in apolipoprotein E4 carriers with mild-moderate Alzheimer's disease","volume":"28","author":"Rosenbloom","year":"2014","journal-title":"CNS Drugs"},{"key":"10.1016\/j.lfs.2017.12.025_bb0575","article-title":"Central nervous system uptake of intranasal glutathione in Parkinson's disease","volume":"2","author":"Mischley","year":"2016","journal-title":"Npj Parkinson's Dis."}],"container-title":["Life Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S002432051730663X?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S002432051730663X?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2022,8,10]],"date-time":"2022-08-10T21:37:35Z","timestamp":1660167455000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S002432051730663X"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,2]]},"references-count":115,"alternative-id":["S002432051730663X"],"URL":"https:\/\/doi.org\/10.1016\/j.lfs.2017.12.025","relation":{},"ISSN":["0024-3205"],"issn-type":[{"value":"0024-3205","type":"print"}],"subject":[],"published":{"date-parts":[[2018,2]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Mechanism of intranasal drug delivery directly to the brain","name":"articletitle","label":"Article Title"},{"value":"Life Sciences","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.lfs.2017.12.025","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2017 Elsevier Inc. All rights reserved.","name":"copyright","label":"Copyright"}]}}