title: Micro CT visualization of silver nanoparticles in the middle and inner ear of rat and transportation pathway after transtympanic injection.
abstract: BACKGROUND
  Silver nanoparticles (Ag NPs) displayed strong activities in anti-bacterial, anti-viral, and anti-fungal studies and were reportedly efficient in treating otitis media. Information on distribution of AgNPs in different compartments of the ear is lacking.
  
  
  OBJECTIVE
  To detect distribution of Ag NPs in the middle and inner ear and transportation pathways after transtympanic injection.
  
  
  METHODS
  Contrast effect of Ag NPs in the micro CT imaging was assessed in a phantom. AgNPs at various concentrations (1.85 mM, 37.1 mM, and 370.7 mM) were administered to rat middle ear using transtympanic injection and cadaver heads were imaged using micro CT at several time points.
  
  
  RESULTS
  The lowest concentration of Ag NPs that could be visualized using micro CT was 37.1 mM. No difference was observed between the solvents, deionized H2O and saline. Ag NPs at 37.1 mM were visible in the middle ear on 7 d post-administration. Ag NPs at 370.7 mM generated signals in the middle ear, ossicular chain, round window membrane, oval window, scala tympani, and Eustachian tube for both 4 h and 24 h time points. A gradient distribution of Ag NPs from the middle ear to the inner ear was detected. The pathways for Ag NPs to be transported from the middle ear into the inner ear are round and oval windows.
  
  
  CONCLUSIONS
  This study provided the imaging evidence that Ag NPs are able to access the inner ear in a dose-dependent manner after intratympanic administration, which is relevant to design the delivery concentration in the future clinic application in order to avoid adverse inner ear effect.
authors.affiliation: Hearing and Balance Research Unit, Field of Oto-laryngology, School of Medicine, University of Tampere, Medisiinarinkatu 3, 33520, Tampere, Finland. Jing.Zou@uta.fi.|Department of Otolaryngology-Head and Neck Surgery, Center for Otolaryngology-Head & Neck Surgery of Chinese PLA, Changhai Hospital, Second Military Medical University, Shanghai, China. Jing.Zou@uta.fi.
authors.forename: Jing
authors.initials: J
authors.lastname: Zou
authors.affiliation: BioMediTech and Department of Electronics and Communications Engineering, Tampere University of Technology, Tampere, Finland. markus.hannula@tut.fi.
authors.forename: Markus
authors.initials: M
authors.lastname: Hannula
authors.affiliation: School of Geography, Earth and Environmental Sciences, University of Birmingham, Birmingham, UK. s.misra@bham.ac.uk.|Materials Science and Engineering, Indian Institute of Technology-Gandhinagar, Ahmedabad, India. s.misra@bham.ac.uk.
authors.forename: Superb
authors.initials: S
authors.lastname: Misra
authors.affiliation: Hearing and Balance Research Unit, Field of Oto-laryngology, School of Medicine, University of Tampere, Medisiinarinkatu 3, 33520, Tampere, Finland. Hao.Feng@uta.fi.
authors.forename: Hao
authors.initials: H
authors.lastname: Feng
authors.affiliation: Nanologica AB, Stockholm, Sweden. hanoi@nanologica.com.
authors.forename: Roberto Hanoi
authors.initials: RH
authors.lastname: Labrador
authors.affiliation: BioMediTech and Department of Electronics and Communications Engineering, Tampere University of Technology, Tampere, Finland. antti.aula@tut.fi.|Department of Medical Physics, Imaging Centre, Tampere University Hospital, Tampere, Finland. antti.aula@tut.fi.
authors.forename: Antti S
authors.initials: AS
authors.lastname: Aula
authors.affiliation: BioMediTech and Department of Electronics and Communications Engineering, Tampere University of Technology, Tampere, Finland. jari.hyttinen@tut.fi.
authors.forename: Jari
authors.initials: J
authors.lastname: Hyttinen
authors.affiliation: Hearing and Balance Research Unit, Field of Oto-laryngology, School of Medicine, University of Tampere, Medisiinarinkatu 3, 33520, Tampere, Finland. Ilmari.Pyykko@uta.fi.
authors.forename: Ilmari
authors.initials: I
authors.lastname: Pyykkö
mesh_terms: D000818:Animals; D003287:Contrast Media; D004305:Dose-Response Relationship, Drug; D007758:Ear, Inner / Q000187:drug effects* / Q000378:metabolism; D004432:Ear, Middle / Q000187:drug effects* / Q000378:metabolism; D000069555:Injection, Intratympanic; D008297:Male; D053768:Metal Nanoparticles / Q000008:administration & dosage* / Q000032:analysis; D010498:Perilymph / Q000187:drug effects; D019047:Phantoms, Imaging; D017207:Rats, Sprague-Dawley; D012680:Sensitivity and Specificity; D012834:Silver / Q000493:pharmacokinetics*; D014018:Tissue Distribution; D055114:X-Ray Microtomography / Q000379:methods*
chemical_list: D003287:Contrast Media; D012834:Silver