{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T21:10:08Z","timestamp":1790111408787,"version":"4.0.1"},"reference-count":42,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T00:00:00Z","timestamp":1788220800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T00:00:00Z","timestamp":1788220800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T00:00:00Z","timestamp":1788220800000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-017"},{"start":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T00:00:00Z","timestamp":1788220800000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-037"},{"start":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T00:00:00Z","timestamp":1788220800000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-012"},{"start":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T00:00:00Z","timestamp":1788220800000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-029"},{"start":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T00:00:00Z","timestamp":1788220800000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-004"}],"content-domain":{"domain":["elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["European Journal of Pharmaceutics and Biopharmaceutics"],"published-print":{"date-parts":[[2026,9]]},"DOI":"10.1016\/j.ejpb.2026.115159","type":"journal-article","created":{"date-parts":[[2026,6,24]],"date-time":"2026-06-24T23:24:24Z","timestamp":1782343464000},"page":"115159","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":0,"special_numbering":"C","title":["Novel approach for direct drug delivery to the central nervous system via intratympanic administration"],"prefix":"10.1016","volume":"226","author":[{"given":"Masayoshi","family":"Saito","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Noriyasu","family":"Sano","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shinji","family":"Nakayama","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuichi","family":"Yokoyama","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naomi","family":"Takeba","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nao","family":"Torimoto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"issue":"12","key":"10.1016\/j.ejpb.2026.115159_b0005","doi-asserted-by":"crossref","first-page":"4","DOI":"10.3389\/fnagi.2020.00004","article-title":"Strategies for the treatment of parkinson\u2019s disease: beyond dopamine","volume":"31","author":"Iarkov","year":"2020","journal-title":"Front. Aging Neurosci."},{"issue":"1","key":"10.1016\/j.ejpb.2026.115159_b0010","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1186\/s12929-023-00976-6","article-title":"Clinical trials of new drugs for Alzheimer disease: a 2020-2023 update","volume":"30","author":"Huang","year":"2023","journal-title":"J. Biomed. Sci."},{"issue":"1","key":"10.1016\/j.ejpb.2026.115159_b0015","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"},{"issue":"8","key":"10.1016\/j.ejpb.2026.115159_b0020","doi-asserted-by":"crossref","first-page":"911","DOI":"10.2174\/138945006778019264","article-title":"Multidrug transporters as drug targets","volume":"7","author":"Liang","year":"2006","journal-title":"Curr. Drug Targets"},{"issue":"9","key":"10.1016\/j.ejpb.2026.115159_b0025","doi-asserted-by":"crossref","first-page":"3309","DOI":"10.1002\/jps.23600","article-title":"Investigation of the effect of active efflux at the blood-brain barrier on the distribution of nonsteroidal aromatase inhibitors in the central nervous system","volume":"102","author":"Miyajima","year":"2013","journal-title":"J. Pharm. Sci."},{"issue":"7","key":"10.1016\/j.ejpb.2026.115159_b0030","doi-asserted-by":"crossref","first-page":"491","DOI":"10.1016\/S2352-4642(21)00100-0","article-title":"Treatment of infantile-onset spinal muscular atrophy with nusinersen: final report of a phase 2, open-label, multicentre, dose-escalation study","volume":"5","author":"Finkel","year":"2021","journal-title":"Lancet Child Adolesc. Health."},{"issue":"2","key":"10.1016\/j.ejpb.2026.115159_b0035","doi-asserted-by":"crossref","first-page":"509","DOI":"10.1016\/j.ymthe.2021.11.005","article-title":"Long-term efficacy and safety of eladocagene exuparvovec in patients with AADC deficiency","volume":"30","author":"Tai","year":"2022","journal-title":"Mol. Ther."},{"key":"10.1016\/j.ejpb.2026.115159_b0040","doi-asserted-by":"crossref","first-page":"25910","DOI":"10.1039\/D5RA03578C","article-title":"Precision targeting of the CNS: recent progress in brain-directed nanodrug delivery","volume":"15","author":"Dinithi","year":"2025","journal-title":"RSC Adv."},{"issue":"2","key":"10.1016\/j.ejpb.2026.115159_b0045","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."},{"issue":"195","key":"10.1016\/j.ejpb.2026.115159_b0050","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":"15","author":"Crowe","year":"2018","journal-title":"Life Sci."},{"issue":"3","key":"10.1016\/j.ejpb.2026.115159_b0055","doi-asserted-by":"crossref","first-page":"604","DOI":"10.1016\/j.juro.2018.04.050","article-title":"Efficacy and safety of SER120 nasal spray in patients with nocturia: pooled analysis of 2 randomized, double-blind, placebo controlled, phase 3 trials","volume":"200","author":"Kaminetsky","year":"2018","journal-title":"J. Urol."},{"issue":"1","key":"10.1016\/j.ejpb.2026.115159_b0060","article-title":"The evaluation of the efficacy and safety of midazolam nasal spray in patients with seizure clusters: a systematic review and meta-analysis","volume":"15","author":"Niraj","year":"2023","journal-title":"Cureus"},{"issue":"3","key":"10.1016\/j.ejpb.2026.115159_b0065","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1016\/0169-409X(93)90015-V","article-title":"The relevance of nasal physiology to the design of drug absorption studies","volume":"11","author":"Gizurarson","year":"1993","journal-title":"Adv. Drug Deliv. Rev."},{"issue":"6","key":"10.1016\/j.ejpb.2026.115159_b0070","doi-asserted-by":"crossref","first-page":"e253","DOI":"10.1002\/ctd2.253","article-title":"Chances and challenges in intranasal administration delivery for brain disease treatment","volume":"3","author":"Shuyu","year":"2023","journal-title":"Clin. Transl. Discov."},{"issue":"4","key":"10.1016\/j.ejpb.2026.115159_b0075","first-page":"352","article-title":"Intratympanic steroid therapy for treatment of idiopathic sudden sensorineural hearing loss","volume":"111","author":"Bear","year":"2014","journal-title":"Mo. Med."},{"key":"10.1016\/j.ejpb.2026.115159_b0080","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1016\/j.heares.2017.12.010","article-title":"Communication pathways to and from the inner ear and their contributions to drug delivery","volume":"362","author":"Salt","year":"2018","journal-title":"Hear. Res."},{"key":"10.1016\/j.ejpb.2026.115159_b0085","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1016\/j.heares.2018.03.002","article-title":"Pharmacokinetic principles in the inner ear: Influence of drug properties on intratympanic applications","volume":"368","author":"Salt","year":"2018","journal-title":"Hear. Res."},{"issue":"3","key":"10.1016\/j.ejpb.2026.115159_b0090","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1530\/EC-14-0076","article-title":"Systemic effects of intratympanic dexamethasone therapy","volume":"3","author":"Eva","year":"2014","journal-title":"Endocr. Connect."},{"issue":"1\u20132","key":"10.1016\/j.ejpb.2026.115159_b0095","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1016\/j.heares.2011.10.003","article-title":"Uptake of gentamicin by vestibular efferent neurons and superior olivary complex after transtympanic administration in guinea pigs","volume":"283","author":"Zhang","year":"2012","journal-title":"Hear. Res."},{"issue":"8","key":"10.1016\/j.ejpb.2026.115159_b0100","doi-asserted-by":"crossref","first-page":"1124","DOI":"10.1097\/MAO.0b013e31815aee21","article-title":"Intratympanic versus intravenous delivery of methylprednisolone to cochlear perilymph","volume":"28","author":"Bird","year":"2007","journal-title":"Otol. Neurotol."},{"issue":"1","key":"10.1016\/j.ejpb.2026.115159_b0105","first-page":"177","article-title":"Neurodegenerative changes in the guinea pig brainstem after intratympanic injection of gentamicin","volume":"813","author":"Jefry","year":"1998","journal-title":"Brain Res."},{"key":"10.1016\/j.ejpb.2026.115159_b0110","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1016\/j.heares.2016.10.003","article-title":"Perilymph pharmacokinetics of locally-applied gentamicin in the guinea pig","volume":"342","author":"Salt","year":"2016","journal-title":"Hear. Res."},{"issue":"9","key":"10.1016\/j.ejpb.2026.115159_b0115","doi-asserted-by":"crossref","first-page":"3862","DOI":"10.1002\/jps.22525","article-title":"Cassette dosing for pharmacokinetic screening in drug discovery: comparison of clearance, volume of distribution, half-life, mean residence time, and oral bioavailability obtained by cassette and discrete dosing in rats","volume":"100","author":"Rakesh","year":"2011","journal-title":"J. Pharm. Sci."},{"issue":"5","key":"10.1016\/j.ejpb.2026.115159_b0120","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1007\/s11095-019-2613-8","article-title":"Direct drug delivery of low-permeable compounds to the central nervous system via intranasal administration in rats and monkeys","volume":"36","author":"Iwasaki","year":"2019","journal-title":"Pharm. Res."},{"issue":"1","key":"10.1016\/j.ejpb.2026.115159_b0125","doi-asserted-by":"crossref","first-page":"15899","DOI":"10.1038\/s41598-017-16019-8","article-title":"Histamine N-methyltransferase regulates aggression and the sleep-wake cycle","volume":"7","author":"Naganuma","year":"2017","journal-title":"Sci. Rep."},{"issue":"1","key":"10.1016\/j.ejpb.2026.115159_b0130","doi-asserted-by":"crossref","first-page":"16451","DOI":"10.1038\/s41598-019-52623-6","article-title":"Histamine H1 receptor on astrocytes and neurons controls distinct aspects of mouse behaviour","volume":"9","author":"K\u00e1rp\u00e1ti","year":"2019","journal-title":"Sci. Rep."},{"issue":"1","key":"10.1016\/j.ejpb.2026.115159_b0135","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1016\/S0165-0270(03)00097-9","article-title":"Determination of histamine in microdialysis samples from rat brain by microbore column liquid chromatography following intramolecular excimer-forming derivatization with pyrene-labeling reagent","volume":"127","author":"Yoshitake","year":"2003","journal-title":"J. Neurosci. Methods"},{"issue":"3","key":"10.1016\/j.ejpb.2026.115159_b0140","first-page":"49","article-title":"Typical and atypical antipsychotic drugs increase extracellular histamine levels in the rat medial prefrontal cortex: contribution of histamine H1 receptor blockade","volume":"17","author":"Fell","year":"2012","journal-title":"Front. Psychiatry"},{"issue":"2","key":"10.1016\/j.ejpb.2026.115159_b0145","doi-asserted-by":"crossref","first-page":"671","DOI":"10.1016\/j.ymthe.2020.09.039","article-title":"A phase 2\/3 trial of pabinafusp alfa, IDS fused with anti-human transferrin receptor antibody, targeting neurodegeneration in MPS-II","volume":"29","author":"Okuyama","year":"2021","journal-title":"Mol. Ther."},{"issue":"1","key":"10.1016\/j.ejpb.2026.115159_b0150","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1111\/j.1365-2125.1994.tb04316.x","article-title":"The effect of enzyme inhibition on the metabolism and activation of tacrine by human liver microsomes","volume":"38","author":"Spaldin","year":"1994","journal-title":"Br. J. Clin. Pharmacol."},{"key":"10.1016\/j.ejpb.2026.115159_b0155","doi-asserted-by":"crossref","first-page":"238","DOI":"10.3389\/fncel.2019.00238","article-title":"Local drug delivery for the treatment of neurotology disorders","volume":"13","author":"Fabrice","year":"2019","journal-title":"Front. Cell. Neurosci."},{"key":"10.1016\/j.ejpb.2026.115159_b0160","first-page":"e018","article-title":"Cochlear aqueduct and its clinical implications","volume":"6","author":"Swain","year":"2025","journal-title":"Ann. Otol. Neurotol."},{"issue":"12","key":"10.1016\/j.ejpb.2026.115159_b0165","doi-asserted-by":"crossref","first-page":"1099","DOI":"10.1056\/NEJMoa2204705","article-title":"Trial of antisense oligonucleotide tofersen for SOD1 ALS","volume":"387","author":"Miller","year":"2022","journal-title":"N. Engl. J. Med."},{"issue":"1","key":"10.1016\/j.ejpb.2026.115159_b0170","doi-asserted-by":"crossref","DOI":"10.1016\/j.omtn.2024.102147","article-title":"Intrathecal administration of a novel siRNA modality extends survival and improves motor function in the SOD1G93A ALS mouse model","volume":"35","author":"Duan","year":"2024","journal-title":"Mol. Ther. Nucleic Acids"},{"issue":"2","key":"10.1016\/j.ejpb.2026.115159_b0175","doi-asserted-by":"crossref","first-page":"1046","DOI":"10.1016\/j.neuroimage.2012.01.065","article-title":"Functional activity mapping of rat auditory pathway after intratympanic manganese administration","volume":"60","author":"Lee","year":"2012","journal-title":"Neuroimage"},{"issue":"6","key":"10.1016\/j.ejpb.2026.115159_b0180","doi-asserted-by":"crossref","first-page":"1085","DOI":"10.1097\/MAO.0b013e31825e7e12","article-title":"Specific targeting of retrocochlear auditory pathway for optimal pharmacotherapy delivery using a mouse model","volume":"33","author":"Dean","year":"2012","journal-title":"Otol. Neurotol."},{"issue":"5","key":"10.1016\/j.ejpb.2026.115159_b0185","doi-asserted-by":"crossref","first-page":"486","DOI":"10.1080\/00016480600895102","article-title":"Transsynaptic delivery of nanoparticles to the central auditory nervous system","volume":"127","author":"Praetorius","year":"2007","journal-title":"Acta Otolaryngol."},{"issue":"7","key":"10.1016\/j.ejpb.2026.115159_b0190","doi-asserted-by":"crossref","first-page":"684","DOI":"10.1002\/chir.20815","article-title":"Stereoselective and multiple carrier-mediated transport of cetirizine across Caco-2 cell monolayers with potential drug interaction","volume":"22","author":"He","year":"2010","journal-title":"Chirality"},{"key":"10.1016\/j.ejpb.2026.115159_b0195","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1016\/j.ejpb.2016.12.027","article-title":"Quantitative analysis of lab-to-lab variability in Caco-2 permeability assays","volume":"114","author":"Lee","year":"2017","journal-title":"Eur. J. Pharm. Biopharm."},{"issue":"1","key":"10.1016\/j.ejpb.2026.115159_b0200","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1111\/j.1476-5381.2011.01547.x","article-title":"Induction of prolonged, continuous slow-wave sleep by blocking cerebral H1 histamine receptors in rats","volume":"165","author":"Ikeda-Sagara","year":"2012","journal-title":"Br. J. Pharmacol."},{"key":"10.1016\/j.ejpb.2026.115159_b0205","article-title":"Isoflurane-induced burst suppression is a thalamus-modulated, focal-onset rhythm with persistent local asynchrony and variable propagation patterns in rats","volume":"14","author":"Ming","year":"2020","journal-title":"Front. Syst. Neurosci."},{"key":"10.1016\/j.ejpb.2026.115159_b0210","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1007\/s40005-022-00586-8","article-title":"Intratympanic drug delivery systems to treat inner ear impairments","volume":"53","author":"Nguyen","year":"2023","journal-title":"J. Pharm. Investig."}],"container-title":["European Journal of Pharmaceutics and Biopharmaceutics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0939641126001803?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0939641126001803?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T20:43:45Z","timestamp":1790109825000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0939641126001803"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9]]},"references-count":42,"alternative-id":["S0939641126001803"],"URL":"https:\/\/doi.org\/10.1016\/j.ejpb.2026.115159","relation":{},"ISSN":["0939-6411"],"issn-type":[{"value":"0939-6411","type":"print"}],"subject":[],"published":{"date-parts":[[2026,9]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Novel approach for direct drug delivery to the central nervous system via intratympanic administration","name":"articletitle","label":"Article Title"},{"value":"European Journal of Pharmaceutics and Biopharmaceutics","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.ejpb.2026.115159","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2026 Elsevier B.V. All rights are reserved, including those for text and data mining, AI training, and similar technologies.","name":"copyright","label":"Copyright"}],"article-number":"115159"}}