title: Size-dependent passage of liposome nanocarriers with preserved posttransport integrity across the middle-inner ear barriers in rats.
abstract: OBJECTIVE
  The goal of this study was to evaluate the impact of liposome nanocarrier size on the efficacy of its transport across the middle-inner ear barriers.
  
  
  METHODS
  The dynamic distribution of liposome nanocarriers encapsulating gadolinium-tetra-azacyclo-dodecane-tetra-acetic acid (LPS+Gd-DOTA) of sizes 95, 130, and 240 nm were observed with a 4.7 T magnetic resonance machine after transtympanic injection in Wistar rats. Histology was performed with confocal microscopy using TRITC conjugated LPS+Gd-DOTA. The integrity of the LPS+Gd-DOTA after transportation was evaluated using cryo-transmission electron microscopy (Cryo-TEM).
  
  
  RESULTS
  Size-dependent transport of the LPS+Gd-DOTA across the middle-inner ear barriers was shown using magnetic resonance imaging, which indicated that the 95-nm nanocarrier showed the significantly highest transport percentage, that the 130-nm nanocarrier showed moderate transport, and that the 240 nm nanocarrier showed the lowest transport. Histologic examinations showed that the LPS+Gd-DOTA were distributed in the epithelial cells of the utricle, capillaries of the spiral ligament, and the spiral ganglion cells. LPS+Gd-DOTA remained intact in the perilymph after transportation.
  
  
  CONCLUSIONS
  The nanocarrier delivery strategy used in this work could be effective in the development of novel inner ear treatments.
authors.affiliation: Department of Otolaryngology, University of Tampere Medical School, Tampere, Finland. Jing.Zou@uta.fi
authors.forename: Jing
authors.initials: J
authors.lastname: Zou
authors.forename: Rohit
authors.initials: R
authors.lastname: Sood
authors.forename: Sanjeev
authors.initials: S
authors.lastname: Ranjan
authors.forename: Dennis
authors.initials: D
authors.lastname: Poe
authors.forename: Usama Abo
authors.initials: UA
authors.lastname: Ramadan
authors.forename: Ilmari
authors.initials: I
authors.lastname: Pyykkö
authors.forename: Paavo K J
authors.initials: PK
authors.lastname: Kinnunen
mesh_terms: D000818:Animals; D003287:Contrast Media; D020285:Cryoelectron Microscopy; D007758:Ear, Inner / Q000378:metabolism; D004432:Ear, Middle / Q000378:metabolism; D006571:Heterocyclic Compounds / Q000008:administration & dosage* / Q000493:pharmacokinetics; D007267:Injections; D008081:Liposomes / Q000378:metabolism; D008279:Magnetic Resonance Imaging; D008297:Male; D046529:Microscopy, Electron, Transmission; D053769:Nanocapsules / Q000008:administration & dosage* / Q000648:ultrastructure; D009942:Organometallic Compounds / Q000008:administration & dosage* / Q000493:pharmacokinetics; D010316:Particle Size; D010498:Perilymph; D051381:Rats; D017208:Rats, Wistar
chemical_list: D003287:Contrast Media; D006571:Heterocyclic Compounds; D008081:Liposomes; D053769:Nanocapsules; D009942:Organometallic Compounds; C050823:gadolinium 1,4,7,10-tetraazacyclododecane-N,N',N'',N'''-tetraacetate