{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T20:33:48Z","timestamp":1792528428024,"version":"4.5.0"},"reference-count":157,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2018,8,3]],"date-time":"2018-08-03T00:00:00Z","timestamp":1533254400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100010661","name":"Horizon 2020 Framework Programme","doi-asserted-by":"publisher","award":["721098"],"award-info":[{"award-number":["721098"]}],"id":[{"id":"10.13039\/100010661","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceutics"],"abstract":"<jats:p>The blood-brain barrier and the blood-cerebrospinal fluid barrier are major obstacles in central nervous system (CNS) drug delivery, since they block most molecules from entering the brain. Alternative drug delivery routes like intraparenchymal or intrathecal are invasive methods with a remaining risk of infections. In contrast, nose-to-brain delivery is a minimally invasive drug administration pathway, which bypasses the blood-brain barrier as the drug is directed from the nasal cavity to the brain. In particular, the skull base located at the roof of the nasal cavity is in close vicinity to the CNS. This area is covered with olfactory mucosa. To design and tailor suitable formulations for nose-to-brain drug delivery, the architecture, structure and physico-chemical characteristics of the mucosa are important criteria. Hence, here we review the state-of-the-art knowledge about the characteristics of the nasal and, in particular, the olfactory mucosa needed for a rational design of intranasal formulations and dosage forms. Also, the information is suitable for the development of systemic or local intranasal drug delivery as well as for intranasal vaccinations.<\/jats:p>","DOI":"10.3390\/pharmaceutics10030116","type":"journal-article","created":{"date-parts":[[2018,8,3]],"date-time":"2018-08-03T11:03:26Z","timestamp":1533294206000},"page":"116","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":431,"title":["Tailoring Formulations for Intranasal Nose-to-Brain Delivery: A Review on Architecture, Physico-Chemical Characteristics and Mucociliary Clearance of the Nasal Olfactory Mucosa"],"prefix":"10.3390","volume":"10","author":[{"given":"Stella","family":"G\u00e4nger","sequence":"first","affiliation":[{"name":"Institute of Applied Biotechnology, University of Applied Sciences Biberach, Hubertus-Liebrecht-Strasse 35, 88400 Biberach, Germany"},{"name":"Faculty of Medicine, University of Ulm, Albert-Einstein-Allee 11, 89081 Ulm, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2514-1654","authenticated-orcid":false,"given":"Katharina","family":"Schindowski","sequence":"additional","affiliation":[{"name":"Institute of Applied Biotechnology, University of Applied Sciences Biberach, Hubertus-Liebrecht-Strasse 35, 88400 Biberach, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2018,8,3]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"104","DOI":"10.1016\/j.addr.2012.10.003","article-title":"Advanced materials and processing for drug delivery: The past and the future","volume":"65","author":"Zhang","year":"2013","journal-title":"Adv. Drug Deliv. Rev."},{"key":"ref_2","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":"ref_3","doi-asserted-by":"crossref","first-page":"614","DOI":"10.1016\/j.addr.2011.11.002","article-title":"Intranasal delivery of biologics to the central nervous system","volume":"64","author":"Lochhead","year":"2012","journal-title":"Adv. Drug Deliv. Rev."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"75","DOI":"10.3109\/10717544.2013.838713","article-title":"Insights into direct nose to brain delivery: Current status and future perspective","volume":"21","author":"Mittal","year":"2014","journal-title":"Drug Deliv."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"62","DOI":"10.1159\/000315319","article-title":"Malfunction of SynchroMed II Baclofen Pump Delivers a Near-Lethal Baclofen Overdose","volume":"46","author":"Sgouros","year":"2010","journal-title":"Pediatr. Neurosurg."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"434","DOI":"10.1097\/AAP.0000000000000132","article-title":"Fentanyl overdose caused by malfunction of SynchroMed II intrathecal pump: Two case reports","volume":"39","author":"Maino","year":"2014","journal-title":"Reg. Anesth. Pain Med."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"232","DOI":"10.3171\/2015.1.PEDS14500","article-title":"Baclofen overdose from possible intrinsic malfunction of SynchroMed II pump","volume":"16","author":"Davanzo","year":"2015","journal-title":"J. Neurosurg. Pediatr."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"64","DOI":"10.3171\/ped.2004.101.2.0064","article-title":"Performance and complications associated with the Synchromed 10-mL infusion pump for intrathecal baclofen administration in children","volume":"101","author":"Albright","year":"2004","journal-title":"J. Neurosurg. Pediatr."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1","DOI":"10.5402\/2012\/575168","article-title":"Complications of Intrathecal Baclofen Pump: Prevention and Cure","volume":"2012","author":"Awaad","year":"2012","journal-title":"ISRN Neurol."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Lochhead, J.J., and Thorne, R.G. (2014). Drug Delivery to the Brain, Springer.","DOI":"10.1007\/978-1-4614-9105-7_14"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1016\/j.lfs.2017.12.025","article-title":"Mechanism of intranasal drug delivery directly to the brain","volume":"195","author":"Crowe","year":"2018","journal-title":"Life Sci."},{"key":"ref_12","first-page":"190","article-title":"Nose-to-Brain delivery of insulin for Alzheimer\u2019s disease","volume":"3","author":"Flamm","year":"2015","journal-title":"ADMET DMPK"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"624","DOI":"10.1016\/j.nut.2009.08.003","article-title":"Intranasal insulin: From nose to brain","volume":"26","author":"Henkin","year":"2010","journal-title":"Nutrition"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1105","DOI":"10.1021\/acs.molpharmaceut.7b00991","article-title":"Delivery of Oxytocin to the Brain for the Treatment of Autism Spectrum Disorder by Nasal Application","volume":"15","author":"Tanaka","year":"2018","journal-title":"Mol. Pharm."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1007\/s11481-016-9687-4","article-title":"Perspectives on Dual Targeting Delivery Systems for Brain Tumors","volume":"12","author":"Gao","year":"2017","journal-title":"J. Neuroimmune Pharmacol."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Dalpiaz, A., and Pavan, B. (2018). Nose-to-brain delivery of antiviral drugs: A way to overcome their active efflux?. Pharmaceutics, 10.","DOI":"10.3390\/pharmaceutics10020039"},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Doty, R.L. (2015). Handbook of Olfaction and Gustation, John Wiley & Sons Inc.. [3rd ed.].","DOI":"10.1002\/9781118971758"},{"key":"ref_18","first-page":"302","article-title":"\u00dcber die Sekretstr\u00f6mung auf der Schleimhaut der oberen Luftwege","volume":"30","author":"Messerklinger","year":"1951","journal-title":"Z. Laryngol. Rhinol. Otol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"S26","DOI":"10.1067\/mai.2001.115563","article-title":"Pharmacokinetics of intranasal corticosteroids","volume":"108","author":"Szefler","year":"2001","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.clinthera.2008.01.005","article-title":"Pharmacokinetic\/pharmacodynamic profile of mometasone furoate nasal spray: Potential effects on clinical safety and efficacy","volume":"30","author":"Hochhaus","year":"2008","journal-title":"Clin. Ther."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1016\/j.pcrj.2005.11.002","article-title":"International Primary Care Respiratory Group (IPCRG) Guidelines: Management of allergic rhinitis","volume":"15","author":"Price","year":"2006","journal-title":"Prim. Care Respir. J."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"487","DOI":"10.1046\/j.1468-2982.1998.1807487.x","article-title":"Sumatriptan Nasal Spray (20 Mg\/Dose) in the Acute Treatment of Cluster Headache","volume":"18","author":"Hardebo","year":"1998","journal-title":"Cephalalgia"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"721","DOI":"10.1177\/0091270003254638","article-title":"Pharmacokinetics of Sumatriptan Nasal Spray in Adolescents","volume":"43","author":"Christensen","year":"2003","journal-title":"J. Clin. Pharmacol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1595","DOI":"10.1164\/rccm.201011-1783OC","article-title":"Potential of nasopharynx-associated lymphoid tissue for vaccine responses in the airways","volume":"183","author":"Brandtzaeg","year":"2011","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"4406","DOI":"10.1016\/j.vaccine.2015.07.022","article-title":"Mucosal vaccination by the intranasal route. Nose-associated lymphoid tissue (NALT)-Structure, function and species differences","volume":"33","author":"Pabst","year":"2015","journal-title":"Vaccine"},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Crespo, C., Liberia, T., Blasco-Ib\u00e1\u00f1ez, J.M., N\u00e1cher, J., and Varea, E. (2018). Cranial pair I: The olfactory nerve. Anat. Rec.","DOI":"10.1002\/ar.23816"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1002\/ar.10047","article-title":"Neural regeneration and the peripheral olfactory system","volume":"269","author":"Schwob","year":"2002","journal-title":"Anat. Rec."},{"key":"ref_28","first-page":"47","article-title":"Stem cells and their niche in the adult olfactory mucosa","volume":"148","year":"2010","journal-title":"Arch. Ital. Biol."},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"French, D.A., Badamdorj, D.D., and Kleene, S.J. (2010). Spatial distribution of calcium-gated chloride channels in olfactory cilia. PLoS ONE, 5.","DOI":"10.1371\/journal.pone.0015676"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"2503","DOI":"10.1016\/j.cub.2015.07.065","article-title":"An Olfactory Cilia Pattern in the Mammalian Nose Ensures High Sensitivity to Odors","volume":"25","author":"Challis","year":"2016","journal-title":"Curr. Biol."},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Trimmer, C., Snyder, L.L., and Mainland, J.D. (2014). High-throughput Analysis of Mammalian Olfactory Receptors: Measurement of Receptor Activation via Luciferase Activity. J. Vis. Exp., 1\u201310.","DOI":"10.3791\/51640"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"274","DOI":"10.1016\/j.cell.2013.09.032","article-title":"Singular expression of olfactory receptor genes","volume":"155","author":"Rodriguez","year":"2013","journal-title":"Cell"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1016\/j.neuroscience.2014.04.050","article-title":"Stereological quantification of olfactory receptor neurons in mice","volume":"272","author":"Kawagishi","year":"2014","journal-title":"Neuroscience"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1347","DOI":"10.1038\/s41467-018-03837-1","article-title":"Stimulus dependent diversity and stereotypy in the output of an olfactory functional unit","volume":"9","author":"Arneodo","year":"2018","journal-title":"Nat. Commun."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"174","DOI":"10.1016\/j.expneurol.2010.08.025","article-title":"Olfactory ensheathing cells from the nose: Clinical application in human spinal cord injuries","volume":"229","year":"2011","journal-title":"Exp. Neurol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"224","DOI":"10.1002\/glia.10160","article-title":"Olfactory ensheathing cells of the lamina propria in vivo and in vitro","volume":"41","author":"Au","year":"2003","journal-title":"Glia"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1016\/j.tins.2003.10.011","article-title":"Olfactory ensheathing cells and CNS repair: Going solo or in need of a friend?","volume":"27","author":"Barnett","year":"2004","journal-title":"Trends Neurosci."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1186\/1742-2094-9-109","article-title":"Cytokines and olfactory bulb microglia in response to bacterial challenge in the compromised primary olfactory pathway","volume":"9","author":"Herbert","year":"2012","journal-title":"J. Neuroinflammation"},{"key":"ref_39","unstructured":"Harris, J.A. (2013). Anti-Bacterial Properties of Olfactory Ensheathing Cells and the Primary Olfactory Pathway. [Ph.D. Thesis, University of Tasmania]."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"940","DOI":"10.1093\/brain\/awn345","article-title":"Live imaging of Toll-like receptor 2 response in cerebral ischaemia reveals a role of olfactory bulb microglia as modulators of inflammation","volume":"132","author":"Phaneuf","year":"2009","journal-title":"Brain"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"674","DOI":"10.1111\/joa.12777","article-title":"Olfactory receptor neuronal dendrites become mostly intra-sustentacularly enwrapped upon maturity","volume":"232","author":"Liang","year":"2018","journal-title":"J. Anat."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"2878","DOI":"10.1111\/ejn.12665","article-title":"Endothelin uncouples gap junctions in sustentacular cells and olfactory ensheathing cells of the olfactory mucosa","volume":"40","author":"Rimbaud","year":"2014","journal-title":"Eur. J. Neurosci."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"11527","DOI":"10.1073\/pnas.0500952102","article-title":"Juxtanodin: An oligodendroglial protein that promotes cellular arborization and 2\u2032,3\u2032-cyclic nucleotide-3\u2032-phosphodiesterase trafficking","volume":"102","author":"Zhang","year":"2005","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"13761","DOI":"10.1523\/JNEUROSCI.1708-15.2015","article-title":"Primary Cilia on Horizontal Basal Cells Regulate Regeneration of the Olfactory Epithelium","volume":"35","author":"Joiner","year":"2015","journal-title":"J. Neurosci."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"1298","DOI":"10.1634\/stemcells.2007-0891","article-title":"Horizontal Basal Cells Are Multipotent Progenitors in Normal and Injured Adult Olfactory Epithelium","volume":"26","author":"Iwai","year":"2008","journal-title":"Stem Cells"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1093\/chemse\/bjr063","article-title":"Aquaporin pathways and mucin secretion of bowman\u2019s glands might protect the olfactory mucosa","volume":"37","author":"Solbu","year":"2012","journal-title":"Chem. Senses"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1007\/BF00582855","article-title":"Licht-und elektronenmikroskopische Befunde zur Struktur der Bowmanschen Dr\u00fcsen im Riechepithel der wei\u00dfen Maus","volume":"131","author":"Breipohl","year":"1972","journal-title":"Zeitschrift f\u00fcr Zellforschung und Mikroskopische Anatomie"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1002\/aja.1001210107","article-title":"Ultrastructure of mouse olfactory mucosa","volume":"121","author":"Frisch","year":"1967","journal-title":"Am. J. Anat."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1002\/jemt.1070230203","article-title":"Fine structural aspects of secretion and extrinsic innervation in the olfactory mucosa","volume":"23","author":"Getchell","year":"1992","journal-title":"Microsc. Res. Tech."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"3216","DOI":"10.1096\/fj.07-104836","article-title":"Impaired olfaction in mice lacking aquaporin-4 water channels","volume":"22","author":"Lu","year":"2008","journal-title":"FASEB J."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1679\/aohc.69.1","article-title":"Immunolocalization of water channel aquaporins in the olfactory mucosa","volume":"69","author":"Ablimit","year":"2006","journal-title":"Arch. Histol. Cytol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1159\/000144835","article-title":"Distribution of epithelia and glands of the nasal septum mucosa in the rat","volume":"99","author":"Katz","year":"1977","journal-title":"Cells Tissues Organs"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"543","DOI":"10.1007\/BF01003270","article-title":"Some histochemical observations on the mucosubstances of the nasal glands of the mouse","volume":"6","author":"Cuschieri","year":"1974","journal-title":"Histochem. J."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"41288","DOI":"10.1074\/jbc.M107257200","article-title":"Aquaporin-5 Dependent Fluid Secretion in Airway Submucosal Glands","volume":"276","author":"Song","year":"2001","journal-title":"J. Biol. Chem."},{"key":"ref_55","first-page":"1315","article-title":"Immunolocalization of antimicrobial and cytoskeletal components in the serous glands of human sinonasal mucosa","volume":"29","author":"Stoeckelhuber","year":"2014","journal-title":"Histol. Histopathol."},{"key":"ref_56","doi-asserted-by":"crossref","unstructured":"Tang, X., Ma, W., Zhan, W., Wang, X., Dong, H., Zhao, H., Yang, L., Ji, C., Han, Q., and Ji, C. (2018). Internal biliary drainage superior to external biliary drainage in improving gut mucosa barrier because of goblet cells and mucin-2 upregulation. Biosci. Rep., BSR20171241.","DOI":"10.1042\/BSR20171241"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"599","DOI":"10.1080\/01926230600865531","article-title":"Normal Structure, Function, and Histology of Mucosa-Associated Lymphoid Tissue","volume":"34","author":"Cesta","year":"2006","journal-title":"Toxicol. Pathol."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1111\/j.1574-695X.2007.00359.x","article-title":"M-cells: Origin, morphology and role in mucosal immunity and microbial pathogenesis","volume":"52","author":"Corr","year":"2008","journal-title":"FEMS Immunol. Med. Microbiol."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"1796","DOI":"10.4049\/jimmunol.168.4.1796","article-title":"Nasal-Associated Lymphoid Tissue Is a Mucosal Inductive Site for Virus-Specific Humoral and Cellular Immune Responses","volume":"168","author":"Zuercher","year":"2002","journal-title":"J. Immunol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"3544","DOI":"10.4161\/hv.36174","article-title":"Roles of M cells in infection and mucosal vaccines","volume":"10","author":"Wang","year":"2014","journal-title":"Hum. Vaccines Immunother."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"2789","DOI":"10.1084\/jem.20070607","article-title":"A novel M cell\u2013specific carbohydrate-targeted mucosal vaccine effectively induces antigen-specific immune responses","volume":"204","author":"Nochi","year":"2007","journal-title":"J. Exp. Med."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1007\/s00441-015-2309-2","article-title":"RANKL regulates differentiation of microfold cells in mouse nasopharynx-associated lymphoid tissue (NALT)","volume":"364","author":"Mutoh","year":"2016","journal-title":"Cell Tissue Res."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1016\/j.it.2017.09.002","article-title":"Vigilance or Subversion? Constitutive and Inducible M Cells in Mucosal Tissues","volume":"39","author":"Lo","year":"2018","journal-title":"Trends Immunol."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"666","DOI":"10.1038\/mi.2013.30","article-title":"Microfold (M) cells: Important immunosurveillance posts in the intestinal epithelium","volume":"6","author":"Mabbott","year":"2013","journal-title":"Mucosal Immunol."},{"key":"ref_65","first-page":"227","article-title":"Current Concepts in Mucosal Immunity","volume":"274","author":"Blumberg","year":"1998","journal-title":"Am. J. Physiol."},{"key":"ref_66","first-page":"144","article-title":"Uptake and translocation of fluorescent latex particles by rabbit Peyer\u2019s patch follicle epithelium: A quantitative model for M cell uptake","volume":"76","author":"Pappo","year":"1989","journal-title":"Clin. Exp. Immunol."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"214","DOI":"10.1016\/j.jaci.2015.07.042","article-title":"Delivery of antigen to nasal-associated lymphoid tissue microfold cells through secretory IgA targeting local dendritic cells confers protective immunity","volume":"137","author":"Rochereau","year":"2016","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_68","doi-asserted-by":"crossref","unstructured":"Selvaraj, K., Gowthamarajan, K., and Karri, V.V.S.R. (2017). Nose to brain transport pathways an overview: Potential of nanostructured lipid carriers in nose to brain targeting. Artif. Cells Nanomed. Biotechnol., 1\u20138.","DOI":"10.1080\/21691401.2017.1420073"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"202","DOI":"10.1111\/j.1749-6632.2009.03894.x","article-title":"The anatomical and electrophysiological basis of peripheral nasal trigeminal chemoreception","volume":"1170","author":"Silver","year":"2009","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1016\/0014-4886(68)90029-0","article-title":"The role of the trigeminal nerve in olfaction","volume":"21","author":"Stone","year":"1968","journal-title":"Exp. Neurol."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"2268","DOI":"10.1093\/cercor\/bhl135","article-title":"Interactions between Olfaction and the Trigeminal System: What Can Be Learned from Olfactory Loss","volume":"17","author":"Frasnelli","year":"2007","journal-title":"Cereb. Cortex"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"2681","DOI":"10.1128\/IAI.00361-16","article-title":"Burkholderia pseudomallei Rapidly Infects the Brain Stem and Spinal Cord via the Trigeminal Nerve after Intranasal Inoculation","volume":"84","author":"Walkden","year":"2016","journal-title":"Infect. Immun."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1007\/s00418-008-0410-2","article-title":"Epithelial and endothelial barriers in the olfactory region of the nasal cavity of the rat","volume":"130","author":"Wolburg","year":"2008","journal-title":"Histochem. Cell Biol."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1093\/chemse\/27.1.7","article-title":"The glucose transporter GLUT1 and the tight junction protein occludin in nasal olfactory mucosa","volume":"27","author":"Hussar","year":"2002","journal-title":"Chem. Senses"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"339","DOI":"10.1007\/s00418-008-0441-8","article-title":"Molecular composition of tight and adherens junctions in the rat olfactory epithelium and fila","volume":"130","author":"Steinke","year":"2008","journal-title":"Histochem. Cell Biol."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"1675","DOI":"10.1007\/s00405-009-1073-x","article-title":"The human olfactory mucosa","volume":"266","author":"Escada","year":"2009","journal-title":"Eur. Arch. Oto-Rhino-Laryngol."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"294","DOI":"10.1002\/path.4843","article-title":"Motile and non-motile cilia in human pathology: From function to phenotypes","volume":"241","author":"Mitchison","year":"2017","journal-title":"J. Pathol."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"12240","DOI":"10.1073\/pnas.96.22.12240","article-title":"Energetic considerations of ciliary beating and the advantage of metachronal coordination","volume":"96","author":"Gueron","year":"1999","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"427","DOI":"10.1007\/s00414-012-0682-x","article-title":"Nasal ciliary motility: A new tool in estimating the time of death","volume":"126","author":"Romanelli","year":"2012","journal-title":"Int. J. Leg. Med."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"527","DOI":"10.1165\/rcmb.2005-0436SF","article-title":"Airway Mucus","volume":"34","author":"Williams","year":"2006","journal-title":"Am. J. Respir. Cell Mol. Biol."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"18327","DOI":"10.1074\/jbc.M008850200","article-title":"MUC13, a Novel Human Cell Surface Mucin Expressed by Epithelial and Hemopoietic Cells","volume":"276","author":"Williams","year":"2001","journal-title":"J. Biol. Chem."},{"key":"ref_82","doi-asserted-by":"crossref","unstructured":"Leal, J., Smyth, H.D.C., and Ghosh, D. (2017). Physicochemical properties of mucus and their impact on transmucosal drug delivery. Int. J. Pharm.","DOI":"10.1016\/j.ijpharm.2017.09.018"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"537","DOI":"10.1042\/bj3610537","article-title":"Heterogeneity of airways mucus: Variations in the amounts and glycoforms of the major oligomeric mucins MUC5AC and MUC5B","volume":"361","author":"Kirkham","year":"2002","journal-title":"Biochem. J."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"412","DOI":"10.1038\/nature12807","article-title":"Muc5b is required for airway defense","volume":"505","author":"Roy","year":"2014","journal-title":"Nature"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1042\/bj3000295","article-title":"A novel human airway mucin cDNA encodes a protein with unique tandem-repeat organization","volume":"300 Pt 2","author":"Shankar","year":"1994","journal-title":"Biochem. J."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1016\/j.addr.2008.09.008","article-title":"Barrier properties of mucus","volume":"61","author":"Cone","year":"2009","journal-title":"Adv. Drug Deliv. Rev."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1146\/annurev.ph.52.030190.001105","article-title":"Goblet Cells Secretion and Mucogenesis","volume":"52","author":"Verdugo","year":"1990","journal-title":"Annu. Rev. Physiol."},{"key":"ref_88","first-page":"212","article-title":"Hydration kinetics of exocytosed mucins in cultured secretory cells of the rabbit trachea: A new model","volume":"109","author":"Verdugo","year":"1984","journal-title":"Ciba Found. Symp."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"525","DOI":"10.1042\/bj2760525","article-title":"Macromolecular properties and polymeric structure of canine tracheal mucins","volume":"276 Pt 2","author":"Shankar","year":"1991","journal-title":"Biochem. J."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"S4","DOI":"10.1164\/ajrccm\/144.3_pt_2.S4","article-title":"The Structure and Heterogeneity of Respiratory Mucus Glycoproteins","volume":"144","author":"Sheehan","year":"1991","journal-title":"Am. Rev. Respir. Dis."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1042\/bj2390147","article-title":"Electron microscopy of cervical, gastric and bronchial mucus glycoproteins","volume":"239","author":"Sheehan","year":"1986","journal-title":"Biochem. J."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"589","DOI":"10.1042\/bj3630589","article-title":"The mouse Muc5b mucin gene: CDNA and genomic structures, chromosomal localization and expression","volume":"363","author":"Escande","year":"2002","journal-title":"Biochem. J."},{"key":"ref_93","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":"Marttin","year":"1998","journal-title":"Adv. Drug Deliv. Rev."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"1930","DOI":"10.1016\/S0006-3495(01)75844-4","article-title":"Diffusion of macromolecules and virus-like particles in human cervical mucus","volume":"81","author":"Olmsted","year":"2001","journal-title":"Biophys. J."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"1482","DOI":"10.1073\/pnas.0608611104","article-title":"Rapid transport of large polymeric nanoparticles in fresh undiluted human mucus","volume":"104","author":"Lai","year":"2007","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1016\/j.ijpharm.2013.05.040","article-title":"Mucus as a barrier to lipophilic drugs","volume":"453","author":"Sigurdsson","year":"2013","journal-title":"Int. J. Pharm."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"1045","DOI":"10.1084\/jem.184.3.1045","article-title":"Role of the glycocalyx in regulating access of microparticles to apical plasma membranes of intestinal epithelial cells: Implications for microbial attachment and oral vaccine targeting","volume":"184","author":"Frey","year":"1996","journal-title":"J. Exp. Med."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"1090","DOI":"10.4049\/jimmunol.175.2.1090","article-title":"Reduced Three-Dimensional Motility in Dehydrated Airway Mucus Prevents Neutrophil Capture and Killing Bacteria on Airway Epithelial Surfaces","volume":"175","author":"Matsui","year":"2005","journal-title":"J. Immunol."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"388","DOI":"10.1046\/j.1365-2273.1998.00173.x","article-title":"Mucociliary transport and its assessment: A review","volume":"23","author":"Lale","year":"1998","journal-title":"Clin. Otolaryngol. Allied Sci."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1111\/bcpt.12342","article-title":"Mucus as a barrier to drug delivery\u2014Understanding and mimicking the barrier properties","volume":"116","author":"Boegh","year":"2015","journal-title":"Basic Clin. Pharmacol. Toxicol."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"314","DOI":"10.1177\/000348949310200412","article-title":"Effects of Nasal Allergen Challenge on Dynamic Viscoelasticity of Nasal Mucus","volume":"102","author":"Hattori","year":"1993","journal-title":"Ann. Otol. Rhinol. Laryngol."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"222","DOI":"10.1183\/09031936.98.11010222","article-title":"Experimental models for studying mucociliary clearance","volume":"11","author":"King","year":"1998","journal-title":"Eur. Respir. J."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"314","DOI":"10.1136\/thorax.55.4.314","article-title":"Analysis of ciliary beat pattern and beat frequency using digital high speed imaging: Comparison with the photomultiplier and photodiode methods","volume":"55","author":"Chilvers","year":"2000","journal-title":"Thorax"},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"508","DOI":"10.1016\/S0006-3495(94)80802-1","article-title":"Antibody diffusion in human cervical mucus","volume":"66","author":"Saltzman","year":"1994","journal-title":"Biophys. J."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"561","DOI":"10.1055\/s-2007-1008498","article-title":"Diagnostic value of nasal secretions, current state: Normal values. 1","volume":"62","author":"Eichner","year":"1983","journal-title":"Laryngol. Rhinol. Otol."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"421","DOI":"10.1164\/ajrccm.160.2.9805117","article-title":"Effect of biochemical components on rheologic properties of nasal mucus in chronic sinusitis","volume":"160","author":"Majima","year":"1999","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_107","first-page":"Doc07","article-title":"Physiology and pathophysiology of respiratory mucosa of the nose and the paranasal sinuses","volume":"9","author":"Beule","year":"2010","journal-title":"GMS Curr. Top. Otorhinolaryngol. Head Neck Surg."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1016\/S0378-5173(99)00442-1","article-title":"Determination of baseline human nasal pH and the effect of intranasally administered buffers","volume":"198","author":"Washington","year":"2000","journal-title":"Int. J. Pharm."},{"key":"ref_109","first-page":"333","article-title":"Nasal mucociliary clearance in perennial rhinitis","volume":"5","author":"Schuhl","year":"1995","journal-title":"J. Investig. Allergol. Clin. Immunol."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/2045-8118-11-10","article-title":"A new look at cerebrospinal fluid circulation","volume":"11","author":"Brinker","year":"2014","journal-title":"Fluids Barriers CNS"},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"4329","DOI":"10.1002\/cne.22459","article-title":"Olfactory ensheathing glia express aquaporin 1","volume":"518","author":"Shields","year":"2010","journal-title":"J. Comp. Neurol."},{"key":"ref_112","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":"ref_113","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":"ref_114","doi-asserted-by":"crossref","first-page":"1159","DOI":"10.1517\/17425247.5.10.1159","article-title":"From nose to brain: Understanding transport capacity and transport rate of drugs","volume":"5","author":"Wu","year":"2008","journal-title":"Expert Opin. Drug Deliv."},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"957","DOI":"10.1517\/17425247.2013.790887","article-title":"Direct nose to brain drug delivery via integrated nerve pathways bypassing the blood-brain barrier: An excellent platform for brain targeting","volume":"10","author":"Pardeshi","year":"2013","journal-title":"Expert Opin. Drug Deliv."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1517\/17425247.2012.636801","article-title":"Physicochemical and physiological considerations for efficient nose-to-brain targeting","volume":"9","author":"Bahadur","year":"2012","journal-title":"Expert Opin. Drug Deliv."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1016\/j.ejpb.2018.05.009","article-title":"Recent advances in carrier mediated nose-to-brain delivery of pharmaceutics","volume":"128","author":"Bourganis","year":"2018","journal-title":"Eur. J. Pharm. Biopharm."},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"1640","DOI":"10.1016\/j.addr.2005.07.009","article-title":"Nasal mucoadhesive drug delivery: Background, applications, trends and future perspectives","volume":"57","author":"Ugwoke","year":"2005","journal-title":"Adv. Drug Deliv. Rev."},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1016\/j.ejpb.2015.11.003","article-title":"Mucoadhesive vs. mucopenetrating particulate drug delivery","volume":"98","author":"Netsomboon","year":"2016","journal-title":"Eur. J. Pharm. Biopharm."},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"655","DOI":"10.1038\/nrd4363","article-title":"Overcoming the challenges in administering biopharmaceuticals: Formulation and delivery strategies","volume":"13","author":"Mitragotri","year":"2014","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"218","DOI":"10.1016\/j.ejpb.2015.05.004","article-title":"Probing the interaction of nanoparticles with mucin for drug delivery applications using dynamic light scattering","volume":"97","author":"Griffiths","year":"2015","journal-title":"Eur. J. Pharm. Biopharm."},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1111\/j.2042-7158.1990.tb05374.x","article-title":"The Effect of Some Preservatives Used in Nasal Preparations on the Mucus and Ciliary Components of Mucociliary Clearance","volume":"42","author":"Batts","year":"1990","journal-title":"J. Pharm. Pharmacol."},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"925","DOI":"10.1111\/j.2042-7158.1993.tb05624.x","article-title":"Ciliotoxicity of methyl- and propyl-p-hydroxybenzoates: A dose-response and surface-response study","volume":"45","author":"Drug","year":"1993","journal-title":"J. Pharm. Pharmacol."},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"957","DOI":"10.1111\/j.1365-2222.1995.tb00398.x","article-title":"The lack of effect of benzalkonium chloride on the cilia of the nasal mucosa in patients with perennial allergic rhinitis: A combined functional, light, scanning and transmission electron microscopy study","volume":"25","author":"Braat","year":"1995","journal-title":"Clin. Exp. Allergy"},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1002\/chir.530050203","article-title":"Ciliotoxicity of intranasal formulations: Menthol enantiomers","volume":"5","author":"Su","year":"1993","journal-title":"Chirality"},{"key":"ref_126","first-page":"1","article-title":"Rhinitis Medicamentosa","volume":"25","author":"Kushnir","year":"2013","journal-title":"Medscape"},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1016\/0378-5173(96)04460-2","article-title":"The effect of nasal drug formulations on ciliary beating in vitro","volume":"135","author":"Romeijn","year":"1996","journal-title":"Int. J. Pharm."},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"E184","DOI":"10.1208\/pt060227","article-title":"Nasal insulin gel as an alternate to parenteral insulin: Formulation, preclinical, and clinical studies","volume":"6","author":"Mutalik","year":"2005","journal-title":"AAPS PharmSciTech"},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"569","DOI":"10.1016\/S1359-6446(02)02255-9","article-title":"Hydrogels: From controlled release to pH-responsive drug delivery","volume":"7","author":"Gupta","year":"2002","journal-title":"Drug Discov. Today"},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"850","DOI":"10.1002\/1520-6017(200007)89:7<850::AID-JPS2>3.0.CO;2-G","article-title":"Bioadhesive-Based Dosage Forms: The Next Generation","volume":"89","author":"Lee","year":"2000","journal-title":"J. Pharm. Sci."},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"570","DOI":"10.1002\/jps.20480","article-title":"Intranasal Mucoadhesive Microemulsions of Clonazepam: Preliminary Studies on Brain Targeting","volume":"95","author":"Vyas","year":"2006","journal-title":"J. Pharm. Sci."},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"E1","DOI":"10.1208\/pt070108","article-title":"Preliminary Brain-targeting Studies on Intranasal Mucoadhesive Microemulsions of Sumatriptan","volume":"7","author":"Vyas","year":"2006","journal-title":"AAPS PharmSciTech"},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"775","DOI":"10.3109\/1061186X.2015.1020809","article-title":"Nanotechnology-mediated nose to brain drug delivery for Parkinson\u2019s disease: A mini review","volume":"23","author":"Kulkarni","year":"2015","journal-title":"J. Drug Target."},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"268","DOI":"10.1016\/j.apsb.2016.05.013","article-title":"Progress and perspectives on targeting nanoparticles for brain drug delivery","volume":"6","author":"Gao","year":"2016","journal-title":"Acta Pharm. Sin. B"},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"628","DOI":"10.1002\/jps.23836","article-title":"Nose-to-Brain Delivery: Evaluation of Polymeric Nanoparticles on Olfactory Ensheathing Cells Uptake","volume":"103","author":"Musumeci","year":"2014","journal-title":"J. Pharm. Sci."},{"key":"ref_136","unstructured":"Schreiber, T., Niedergall, K., Wojciukiewicz, D., Gose, T., Gruber-Traub, C., Weber, A., Hirth, T., and Tovar, G. (2010). NANOCYTES-Technology\u2014Biomimetic nanoparticles for molecular recognition by molecular imprinting. Bio Sensors, Instruments, Medical, Environment and Energy: An Interdisciplinary Integrative Forum on Nanotechnology, Biotechnology and Mic (Volume 3), Proceedings of the 2010 NSTI Nanotechnology Conference and Expo-Nanotech Conference & Expo 2010, Berlin, Germany, 20\u201322 October 2010, CRC Press."},{"key":"ref_137","doi-asserted-by":"crossref","first-page":"411","DOI":"10.1016\/j.addr.2004.09.004","article-title":"Biodegradable mucoadhesive particulates for nasal and pulmonary antigen and DNA delivery","volume":"57","author":"Alpar","year":"2005","journal-title":"Adv. Drug Deliv. Rev."},{"key":"ref_138","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1016\/j.ijbiomac.2015.07.041","article-title":"Brain delivery of buspirone hydrochloride chitosan nanoparticles for the treatment of general anxiety disorder","volume":"81","author":"Bari","year":"2015","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_139","doi-asserted-by":"crossref","unstructured":"Thanh, N.T.K. (2018). Good Manufacturing Practices (GMP) of Magnetic nanoparticles. Clinical Applications of Magnetic Nanoparticles, Taylor and Francis.","DOI":"10.1201\/9781315168258"},{"key":"ref_140","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1016\/j.ijpharm.2013.08.079","article-title":"Nanocarriers for intravenous injection\u2014The long hard road to the market","volume":"457","author":"Wacker","year":"2013","journal-title":"Int. J. Pharm."},{"key":"ref_141","doi-asserted-by":"crossref","first-page":"363","DOI":"10.1016\/j.ejpb.2017.04.032","article-title":"Ciprofloxacin-loaded PLGA nanoparticles against cystic fibrosis P. aeruginosa lung infections","volume":"117","author":"Torge","year":"2017","journal-title":"Eur. J. Pharm. Biopharm."},{"key":"ref_142","doi-asserted-by":"crossref","first-page":"343","DOI":"10.1016\/j.ijpharm.2016.10.025","article-title":"Optimization of ciprofloxacin complex loaded PLGA nanoparticles for pulmonary treatment of cystic fibrosis infections: Design of experiments approach","volume":"515","author":"Schneider","year":"2016","journal-title":"Int. J. Pharm."},{"key":"ref_143","doi-asserted-by":"crossref","first-page":"393","DOI":"10.1016\/j.ejps.2012.12.007","article-title":"Bromocriptine loaded chitosan nanoparticles intended for direct nose to brain delivery: Pharmacodynamic, Pharmacokinetic and Scintigraphy study in mice model","volume":"48","author":"Shadab","year":"2013","journal-title":"Eur. J. Pharm. Sci."},{"key":"ref_144","doi-asserted-by":"crossref","first-page":"453","DOI":"10.1016\/j.jddst.2017.11.013","article-title":"Chitosan-Mangafodipir nanoparticles designed for intranasal delivery of siRNA and DNA to brain","volume":"43","author":"Song","year":"2018","journal-title":"J. Drug Deliv. Sci. Technol."},{"key":"ref_145","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1016\/j.ejpb.2014.12.006","article-title":"Biodistribution of nanostructured lipid carriers: A tomographic study","volume":"89","author":"Esposito","year":"2015","journal-title":"Eur. J. Pharm. Biopharm."},{"key":"ref_146","doi-asserted-by":"crossref","first-page":"431","DOI":"10.3389\/fimmu.2018.00431","article-title":"Lipid-based particles: Versatile delivery systems for mucosal vaccination against infection","volume":"9","author":"Bioley","year":"2018","journal-title":"Front. Immunol."},{"key":"ref_147","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1016\/S0378-4274(03)00023-7","article-title":"Toxicity to nasal-associated lymphoid tissue","volume":"140\u2013141","author":"Kuper","year":"2003","journal-title":"Toxicol. Lett."},{"key":"ref_148","doi-asserted-by":"crossref","first-page":"643","DOI":"10.1001\/archotol.134.6.643","article-title":"Intranasal administration of drugs","volume":"134","author":"Scheibe","year":"2008","journal-title":"Arch. Otolaryngol. Head. Neck Surg."},{"key":"ref_149","doi-asserted-by":"crossref","first-page":"831","DOI":"10.1093\/chemse\/27.9.831","article-title":"Intranasal volume and olfactory function","volume":"27","author":"Damm","year":"2002","journal-title":"Chem. Senses"},{"key":"ref_150","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1016\/j.physbeh.2012.12.007","article-title":"Size of nostril opening as a measure of intranasal volume","volume":"110\u2013111","author":"Schriever","year":"2013","journal-title":"Physiol. Behav."},{"key":"ref_151","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/s11095-016-1875-7","article-title":"First Steps to Develop and Validate a CFPD Model in Order to Support the Design of Nose-to-Brain Delivered Biopharmaceuticals","volume":"33","author":"Engelhardt","year":"2016","journal-title":"Pharm. Res."},{"key":"ref_152","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":"ref_153","doi-asserted-by":"crossref","first-page":"125","DOI":"10.2147\/DDDT.S25199","article-title":"Novel drug-delivery systems for patients with chronic rhinosinusitis","volume":"6","author":"Albu","year":"2012","journal-title":"Drug Des. Devel. Ther."},{"key":"ref_154","doi-asserted-by":"crossref","first-page":"864","DOI":"10.1212\/01.wnl.0000327291.47162.ed","article-title":"Intranasal insulin improves cognition and modulates beta-amyloid in early AD","volume":"71","author":"Djupesland","year":"2008","journal-title":"Neurology"},{"key":"ref_155","doi-asserted-by":"crossref","first-page":"466","DOI":"10.1097\/01.MLG.0000199741.08517.99","article-title":"Breath actuated device improves delivery to target sites beyond the nasal valve","volume":"116","author":"Djupesland","year":"2006","journal-title":"Laryngoscope"},{"key":"ref_156","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1089\/jam.2004.17.249","article-title":"Bi-directional nasal delivery of aerosols can prevent lung deposition","volume":"17","author":"Djupesland","year":"2004","journal-title":"J. Aerosol Med."},{"key":"ref_157","doi-asserted-by":"crossref","first-page":"641","DOI":"10.1213\/ANE.0b013e3182239b8c","article-title":"Enhanced analgesic responses after preferential delivery of morphine and fentanyl to the olfactory epithelium in rats","volume":"113","author":"Hoekman","year":"2011","journal-title":"Anesth. Analg."}],"container-title":["Pharmaceutics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1999-4923\/10\/3\/116\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T15:16:32Z","timestamp":1760195792000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1999-4923\/10\/3\/116"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,8,3]]},"references-count":157,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2018,9]]}},"alternative-id":["pharmaceutics10030116"],"URL":"https:\/\/doi.org\/10.3390\/pharmaceutics10030116","relation":{},"ISSN":["1999-4923"],"issn-type":[{"value":"1999-4923","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,8,3]]}}}