{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T03:45:35Z","timestamp":1790221535698,"version":"4.1.0"},"reference-count":48,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2019,1,1]],"date-time":"2019-01-01T00:00:00Z","timestamp":1546300800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81573618"],"award-info":[{"award-number":["81573618"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003453","name":"Natural Science Foundation of Guangdong Province","doi-asserted-by":"publisher","award":["2017A030313653"],"award-info":[{"award-number":["2017A030313653"]}],"id":[{"id":"10.13039\/501100003453","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["European Journal of Pharmaceutical Sciences"],"published-print":{"date-parts":[[2019,1]]},"DOI":"10.1016\/j.ejps.2018.02.031","type":"journal-article","created":{"date-parts":[[2018,2,27]],"date-time":"2018-02-27T23:13:16Z","timestamp":1519773196000},"page":"11-22","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":29,"special_numbering":"C","title":["Is oval window transport a royal gate for nanoparticle delivery to vestibule in the inner ear?"],"prefix":"10.1016","volume":"126","author":[{"given":"Shan","family":"Ding","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shibao","family":"Xie","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weiquan","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lu","family":"Wen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junyi","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fan","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gang","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.ejps.2018.02.031_bb0005","doi-asserted-by":"crossref","first-page":"5591","DOI":"10.2147\/IJN.S72555","article-title":"Enhanced local bioavailability of single or compound drugs delivery to the inner ear through application of PLGA nanoparticles via round window administration","volume":"9","author":"Cai","year":"2014","journal-title":"Int. J. Nanomedicine"},{"key":"10.1016\/j.ejps.2018.02.031_bb0010","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1016\/j.ijpharm.2017.08.084","article-title":"Engineering PLGA nano-based systems through understanding the influence of nanoparticle properties and cell-penetrating peptides for cochlear drug delivery","volume":"532","author":"Cai","year":"2017","journal-title":"Int. J. Pharm."},{"key":"10.1016\/j.ejps.2018.02.031_bb0015","doi-asserted-by":"crossref","first-page":"886","DOI":"10.2174\/138920010794479673","article-title":"Disposition of nanoparticle-based delivery system via inner ear administration","volume":"11","author":"Chen","year":"2010","journal-title":"Curr. Drug Metab."},{"key":"10.1016\/j.ejps.2018.02.031_bb0020","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1016\/S0378-5173(01)00760-8","article-title":"Chitosan nanoparticles: a new vehicle for the improvement of the delivery of drugs to the ocular surface. Application to cyclosporin A","volume":"224","author":"De Campos","year":"2001","journal-title":"Int. J. Pharm."},{"key":"10.1016\/j.ejps.2018.02.031_bb0025","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1097\/MAO.0b013e318277a40e","article-title":"Magnetic targeted delivery of dexamethasone acetate across the round window membrane in guinea pigs","volume":"34","author":"Du","year":"2013","journal-title":"Otol. Neurotol."},{"key":"10.1016\/j.ejps.2018.02.031_bb0030","doi-asserted-by":"crossref","first-page":"7915","DOI":"10.1073\/pnas.0812446106","article-title":"MicroRNAs are essential for development and function of inner ear hair cells in vertebrates","volume":"106","author":"Friedman","year":"2009","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"10.1016\/j.ejps.2018.02.031_bb0035","doi-asserted-by":"crossref","first-page":"897","DOI":"10.1021\/bc049951i","article-title":"Toxicity of gold nanoparticles functionalized with cationic and anionic side chains","volume":"15","author":"Goodman","year":"2004","journal-title":"Bioconjug. Chem."},{"key":"10.1016\/j.ejps.2018.02.031_bb0040","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1002\/(SICI)1097-0029(19970201)36:3<201::AID-JEMT8>3.0.CO;2-R","article-title":"Round window membrane. Structure function and permeability: a review","volume":"36","author":"Goycoolea","year":"1997","journal-title":"Microsc. Res. Tech."},{"key":"10.1016\/j.ejps.2018.02.031_bb0045","doi-asserted-by":"crossref","first-page":"1747","DOI":"10.1016\/j.apmr.2015.04.003","article-title":"Measurement characteristics and clinical utility of the clinical test of sensory interaction on balance (CTSIB) and modified CTSIB in individuals with vestibular dysfunction","volume":"96","author":"Horn","year":"2015","journal-title":"Arch. Phys. Med. Rehabil."},{"key":"10.1016\/j.ejps.2018.02.031_bb0050","doi-asserted-by":"crossref","first-page":"115","DOI":"10.4155\/tde.12.130","article-title":"Drug delivery to the ear","volume":"4","author":"Hoskison","year":"2013","journal-title":"Ther. Deliv."},{"key":"10.1016\/j.ejps.2018.02.031_bb0055","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1038\/scientificamerican0183-54","article-title":"The hair cells of the inner ear","volume":"248","author":"Hudspeth","year":"1983","journal-title":"Sci. Am."},{"key":"10.1016\/j.ejps.2018.02.031_bb0060","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1159\/000071059","article-title":"A cochlear cell line as an in vitro system for drug ototoxicity screening","volume":"8","author":"Kalinec","year":"2003","journal-title":"Audiol. Neurootol."},{"key":"10.1016\/j.ejps.2018.02.031_bb0065","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1177\/000348947108000104","article-title":"Fine structure of the round window membrane","volume":"80","author":"Kawabata","year":"1971","journal-title":"Ann. Otol. Rhinol. Laryngol."},{"key":"10.1016\/j.ejps.2018.02.031_bb0070","doi-asserted-by":"crossref","first-page":"741","DOI":"10.1007\/s10162-011-0280-5","article-title":"Direct entry of gadolinium into the vestibule following intratympanic applications in Guinea pigs and the influence of cochlear implantation","volume":"12","author":"King","year":"2011","journal-title":"J. Assoc. Res. Otolaryngol."},{"key":"10.1016\/j.ejps.2018.02.031_bb0075","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1016\/j.heares.2013.07.013","article-title":"Gentamicin administration on the stapes footplate causes greater hearing loss and vestibulotoxicity than round window administration in guinea pigs","volume":"304","author":"King","year":"2013","journal-title":"Hear. Res."},{"key":"10.1016\/j.ejps.2018.02.031_bb0080","doi-asserted-by":"crossref","first-page":"341","DOI":"10.1097\/MAO.0000000000000445","article-title":"A novel chitosan-hydrogel-based nanoparticle delivery system for local inner ear application","volume":"36","author":"Lajud","year":"2015","journal-title":"Otol. Neurotol."},{"key":"10.1016\/j.ejps.2018.02.031_bb0085","doi-asserted-by":"crossref","first-page":"10,799","DOI":"10.1021\/nn4040553","article-title":"Cell membranes open \u201cdoors\u201d for cationic nanoparticles\/biomolecules: insights into uptake kinetics","volume":"7","author":"Lin","year":"2013","journal-title":"ACS Nano"},{"key":"10.1016\/j.ejps.2018.02.031_bb0090","doi-asserted-by":"crossref","first-page":"846","DOI":"10.3109\/1061186X.2013.829075","article-title":"The effect of surface charge of glycerol monooleate-based nanoparticles on the round window membrane permeability and cochlear distribution","volume":"21","author":"Liu","year":"2013","journal-title":"J. Drug Target."},{"key":"10.1016\/j.ejps.2018.02.031_bb0095","doi-asserted-by":"crossref","first-page":"472","DOI":"10.3109\/00016488709128277","article-title":"Round window membrane permeability. An in vitro model","volume":"104","author":"Lundman","year":"1987","journal-title":"Acta Otolaryngol."},{"key":"10.1016\/j.ejps.2018.02.031_bb0100","doi-asserted-by":"crossref","first-page":"250","DOI":"10.1016\/j.neures.2007.03.006","article-title":"Cochlear expression of a dominant-negative GJB2 (R75W) construct delivered through the round window membrane in mice","volume":"58","author":"Maeda","year":"2007","journal-title":"Neurosci. Res."},{"key":"10.1016\/j.ejps.2018.02.031_bb0105","doi-asserted-by":"crossref","first-page":"179","DOI":"10.3109\/03005369009076554","article-title":"Cochlear and cerebrospinal fluid pressure: their inter-relationship and control mechanisms","volume":"24","author":"Marchbanks","year":"1990","journal-title":"Br. J. Audiol."},{"key":"10.1016\/j.ejps.2018.02.031_bb0110","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1007\/s00795-007-0394-3","article-title":"Histochemical localization of the extracellular matrix components in the annular ligament of rat stapediovestibular joint with special reference to fbrillin, 36-kDa microfbril-associated glycoprotein (MAGP-36), and hyaluronic acid","volume":"41","author":"Ohashi","year":"2008","journal-title":"Med. Mol. Morphol."},{"key":"10.1016\/j.ejps.2018.02.031_bb0115","doi-asserted-by":"crossref","first-page":"353","DOI":"10.1097\/MAO.0b013e31827ca330","article-title":"\u201cIn-bone\u201d utricle cultures-A simplified, atraumatic technique for in situ cultures of the adult mouse (Mus musculus) utricle","volume":"34","author":"Ou","year":"2013","journal-title":"Otol. Neurotol."},{"key":"10.1016\/j.ejps.2018.02.031_bb0120","doi-asserted-by":"crossref","first-page":"706","DOI":"10.1097\/MLG.0b013e31815f8e41","article-title":"A novel controlled local drug delivery system for inner ear disease","volume":"118","author":"Paulson","year":"2008","journal-title":"Laryngoscope"},{"key":"10.1016\/j.ejps.2018.02.031_bb0125","doi-asserted-by":"crossref","first-page":"72","DOI":"10.1159\/000442514","article-title":"Intracochlear drug injections through the round window membrane: measures to improve drug retention","volume":"21","author":"Plontke","year":"2016","journal-title":"Audiol. Neurootol."},{"key":"10.1016\/j.ejps.2018.02.031_bb9500","doi-asserted-by":"crossref","first-page":"486","DOI":"10.1080\/00016480600895102","article-title":"Transsynaptic delivery of nanoparticles to the central auditory nervous","volume":"127","author":"Praetorius","year":"2007","journal-title":"Acta Otolaryngol."},{"key":"10.1016\/j.ejps.2018.02.031_bb0130","doi-asserted-by":"crossref","first-page":"1155","DOI":"10.2217\/nnm.13.104","article-title":"Nanomedicine strategies for drug delivery to the ear","volume":"8","author":"Pritz","year":"2013","journal-title":"Nanomedicine (London)"},{"key":"10.1016\/j.ejps.2018.02.031_bb0135","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1038\/gt.2013.49","article-title":"Efficient siRNA transfection to the inner ear through the intact round window by a novel proteidic delivery technology in the chinchilla","volume":"21","author":"Qi","year":"2014","journal-title":"Gene Ther."},{"key":"10.1016\/j.ejps.2018.02.031_bb0140","doi-asserted-by":"crossref","first-page":"110","DOI":"10.1016\/j.ejps.2009.11.003","article-title":"Use of the biodegradable polymer chitosan as a vehicle for applying drugs to the inner ear","volume":"39","author":"Saber","year":"2010","journal-title":"Eur. J. Pharm. Sci."},{"key":"10.1016\/j.ejps.2018.02.031_bb0145","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1016\/j.heares.2011.11.012","article-title":"Marker entry into vestibular perilymph via the stapes following applications to the round window niche of Guinea pigs","volume":"283","author":"Salt","year":"2012","journal-title":"Hear. Res."},{"key":"10.1016\/j.ejps.2018.02.031_bb0150","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1007\/s10162-015-0512-1","article-title":"Perilymph kinetics of FITC-dextran reveals homeostasis dominated by the cochlear aqueduct and cerebrospinal fluid","volume":"16","author":"Salt","year":"2015","journal-title":"J. Assoc. Res. Otolaryngol."},{"key":"10.1016\/j.ejps.2018.02.031_bb0155","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."},{"key":"10.1016\/j.ejps.2018.02.031_bb0160","doi-asserted-by":"crossref","first-page":"55","DOI":"10.2217\/nnm.11.84","article-title":"Strategies for drug delivery to the human inner ear by multifunctional nanoparticles","volume":"7","author":"Saulnier","year":"2012","journal-title":"Nanomedicine"},{"key":"10.1016\/j.ejps.2018.02.031_bb0165","doi-asserted-by":"crossref","first-page":"550","DOI":"10.1001\/archotol.1982.00790570016004","article-title":"The normal chinchilla round window membrane","volume":"108","author":"Schachern","year":"1982","journal-title":"Arch. Otolaryngol."},{"key":"10.1016\/j.ejps.2018.02.031_bb0170","doi-asserted-by":"crossref","first-page":"623","DOI":"10.2217\/nnm.09.41","article-title":"Potential novel drug carriers for inner ear treatment: hyperbranched polylysine and lipid nanocapsules","volume":"4","author":"Scheper","year":"2009","journal-title":"Nanomedicine"},{"key":"10.1016\/j.ejps.2018.02.031_bb0175","doi-asserted-by":"crossref","first-page":"859","DOI":"10.1288\/00005537-195607000-00005","article-title":"Ablation therapy for the relief of Meniere's disease","volume":"66","author":"Schuknecht","year":"1956","journal-title":"Laryngoscope"},{"key":"10.1016\/j.ejps.2018.02.031_bb0180","doi-asserted-by":"crossref","first-page":"888","DOI":"10.1177\/019459987908700625","article-title":"The penetration of gentamicin and neomycin into perilymph across the round window membrane","volume":"87","author":"Smith","year":"1979","journal-title":"Otolaryngol. Head Neck Surg."},{"key":"10.1016\/j.ejps.2018.02.031_bb0185","doi-asserted-by":"crossref","first-page":"8712","DOI":"10.1016\/j.biomaterials.2011.07.086","article-title":"Effects of chitosan-nanoparticle-mediated tight junction opening on the oral absorption of endotoxins","volume":"32","author":"Sonaje","year":"2011","journal-title":"Biomaterials"},{"key":"10.1016\/j.ejps.2018.02.031_bb0190","first-page":"51","article-title":"In vitro and in vivo studies on hydroxyapatite nanoparticles as a novel vector for inner ear gene therapy","volume":"43","author":"Sun","year":"2008","journal-title":"Zhonghua Er Bi Yan Hou Tou Jing Wai Ke Za Zhi"},{"key":"10.1016\/j.ejps.2018.02.031_bb0195","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1007\/BF00464276","article-title":"Permeability of the labyrinthine windows in guinea pigs","volume":"233","author":"Tanaka","year":"1981","journal-title":"Arch. Otorhinolaryngol."},{"key":"10.1016\/j.ejps.2018.02.031_bb0200","doi-asserted-by":"crossref","first-page":"5959","DOI":"10.2147\/IJN.S116867","article-title":"Nanomedicine strategy for optimizing delivery to outer hair cells by surface-modified poly (lactic\/glycolic acid) nanoparticles with hydrophilic molecules","volume":"11","author":"Wen","year":"2016","journal-title":"Int. J. Nanomedicine"},{"key":"10.1016\/j.ejps.2018.02.031_bb0205","doi-asserted-by":"crossref","first-page":"595","DOI":"10.1016\/j.ejps.2013.01.007","article-title":"Novel multiple agents loaded PLGA nanoparticles for brain delivery via inner ear administration: in vitro and in vivo evaluation","volume":"48","author":"Zhang","year":"2013","journal-title":"Eur. J. Pharm. Sci."},{"key":"10.1016\/j.ejps.2018.02.031_bb0210","first-page":"2769","article-title":"Biocompatible nanocarriers that respond to oxidative environments via interactions between chitosan and multiple metal ions","volume":"11","author":"Zhang","year":"2016","journal-title":"Int. J. Nanomedicine"},{"key":"10.1016\/j.ejps.2018.02.031_bb0215","doi-asserted-by":"crossref","first-page":"3082","DOI":"10.3109\/10717544.2016.1149745","article-title":"Mathematical modeling for local trans-round window membrane drug transport in the inner ear","volume":"23","author":"Zhang","year":"2016","journal-title":"Drug Deliv."},{"key":"10.1016\/j.ejps.2018.02.031_bb0220","doi-asserted-by":"crossref","first-page":"388","DOI":"10.1016\/j.lfs.2006.09.040","article-title":"Chitosan nanoparticle as gene therapy vector via gastrointestinal mucosa administration: results of an in vitro and in vivo study","volume":"80","author":"Zheng","year":"2007","journal-title":"Life Sci."},{"key":"10.1016\/j.ejps.2018.02.031_bb0225","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1159\/000084024","article-title":"Communication between the perilymphatic scalae and spiral ligament visualized by in vivo MRI","volume":"10","author":"Zou","year":"2005","journal-title":"Audiol. Neurotol."},{"key":"10.1016\/j.ejps.2018.02.031_bb0230","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1177\/000348941212100209","article-title":"Oval window transport of Gd-DOTA from rat middle ear to vestibulum and scala vestibuli visualized by in vivo magnetic resonance imaging","volume":"121","author":"Zou","year":"2012","journal-title":"Ann. Otol. Rhinol. Laryngol."},{"key":"10.1016\/j.ejps.2018.02.031_bb0235","doi-asserted-by":"crossref","first-page":"1883","DOI":"10.1002\/jbm.b.33719","article-title":"Efficient penetration of ceric ammonium nitrate oxidant-stabilized gamma-maghemite nanoparticles through the oval and round windows into the rat inner ear as demonstrated by MRI","volume":"105","author":"Zou","year":"2017","journal-title":"J Biomed Mater Res B Appl Biomater"}],"container-title":["European Journal of Pharmaceutical Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0928098718301088?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0928098718301088?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2018,11,12]],"date-time":"2018-11-12T13:11:13Z","timestamp":1542028273000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0928098718301088"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,1]]},"references-count":48,"alternative-id":["S0928098718301088"],"URL":"https:\/\/doi.org\/10.1016\/j.ejps.2018.02.031","relation":{},"ISSN":["0928-0987"],"issn-type":[{"value":"0928-0987","type":"print"}],"subject":[],"published":{"date-parts":[[2019,1]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Is oval window transport a royal gate for nanoparticle delivery to vestibule in the inner ear?","name":"articletitle","label":"Article Title"},{"value":"European Journal of Pharmaceutical Sciences","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.ejps.2018.02.031","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2018 Published by Elsevier B.V.","name":"copyright","label":"Copyright"}]}}