title: Superparamagnetic nanoparticles as vectors for inner ear treatments: driving and toxicity evaluation.
abstract: Conclusion Super paramagnetic nanoparticles (MNP) are a promising vector to achieve controlled drug delivery into the cochlea. Objective The goal of the study was to evaluate the toxicological risk of MNP upon the inner ear. Methods Fe3O4-MNP displacement was studied in various catheter materials, shape, and solvent with a local magnetic field. EC5V cells (derived from the inner ear) were cultured with MNP (100 and 500 nm) at various concentrations or without MNP. Cell survival was assessed with a flow cytometry analysis. Localization of MNP within the cells was studied with confocal microscopy. In vivo, a single intra-cochlear administration of 200 nm MNP (3 × 10(10)MNP/mL, n = 8; 1.5 × 10(12) MNP/mL, n = 6) or saline (n = 14) was performed in guinea pigs. Hearing thresholds were assessed with auditory brainstem responses at Day 7. Results MNP could be concentrated at different locations of the catheter with sequential activation of solenoids. MNP were internalized in the cytoplasm, but not in the nuclei nor in endosomes at 48 h. After 48 h of incubation, no difference for cell survival between the groups was observed, whatever the MNP concentration. A size effect was observed with less survival in the 100 nm group. In guinea pigs at day 7, hearing threshold shift was not different in the three groups.
authors.affiliation: a Inserm, 'Minimally Invasive Robot-based Hearing Rehabilitation', UMR-S 1159 , Paris , France ;|b Sorbonne University, University Pierre et Marie Curie, UPMC Univ Paris 06 , Paris , France ;|c Otolaryngology Department , Unit of Otology, Auditory Implants and Skull Base Surgery, Hospital Pitié Salpêtrière, 47-83 boulevard de l'Hôpital, Cedex 13, , Paris , France ;
authors.forename: Yann
authors.initials: Y
authors.lastname: Nguyen
authors.affiliation: a Inserm, 'Minimally Invasive Robot-based Hearing Rehabilitation', UMR-S 1159 , Paris , France ;|b Sorbonne University, University Pierre et Marie Curie, UPMC Univ Paris 06 , Paris , France ;|c Otolaryngology Department , Unit of Otology, Auditory Implants and Skull Base Surgery, Hospital Pitié Salpêtrière, 47-83 boulevard de l'Hôpital, Cedex 13, , Paris , France ;
authors.forename: Charlotte
authors.initials: C
authors.lastname: Celerier
authors.affiliation: a Inserm, 'Minimally Invasive Robot-based Hearing Rehabilitation', UMR-S 1159 , Paris , France ;|b Sorbonne University, University Pierre et Marie Curie, UPMC Univ Paris 06 , Paris , France ;|c Otolaryngology Department , Unit of Otology, Auditory Implants and Skull Base Surgery, Hospital Pitié Salpêtrière, 47-83 boulevard de l'Hôpital, Cedex 13, , Paris , France ;
authors.forename: Romain
authors.initials: R
authors.lastname: Pszczolinski
authors.affiliation: d Inserm 'Kidney Immunopathology, Receptors and Inflammation", UMR-S 1149 , Paris , France.
authors.forename: Julien
authors.initials: J
authors.lastname: Claver
authors.affiliation: d Inserm 'Kidney Immunopathology, Receptors and Inflammation", UMR-S 1149 , Paris , France.
authors.forename: Ulrick
authors.initials: U
authors.lastname: Blank
authors.affiliation: a Inserm, 'Minimally Invasive Robot-based Hearing Rehabilitation', UMR-S 1159 , Paris , France ;|b Sorbonne University, University Pierre et Marie Curie, UPMC Univ Paris 06 , Paris , France ;|c Otolaryngology Department , Unit of Otology, Auditory Implants and Skull Base Surgery, Hospital Pitié Salpêtrière, 47-83 boulevard de l'Hôpital, Cedex 13, , Paris , France ;
authors.forename: Evelyne
authors.initials: E
authors.lastname: Ferrary
authors.affiliation: a Inserm, 'Minimally Invasive Robot-based Hearing Rehabilitation', UMR-S 1159 , Paris , France ;|b Sorbonne University, University Pierre et Marie Curie, UPMC Univ Paris 06 , Paris , France ;|c Otolaryngology Department , Unit of Otology, Auditory Implants and Skull Base Surgery, Hospital Pitié Salpêtrière, 47-83 boulevard de l'Hôpital, Cedex 13, , Paris , France ;
authors.forename: Olivier
authors.initials: O
authors.lastname: Sterkers
mesh_terms: D000818:Animals; D002460:Cell Line; D016503:Drug Delivery Systems; D007758:Ear, Inner / Q000187:drug effects*; D006168:Guinea Pigs; D006309:Hearing / Q000187:drug effects*; D058185:Magnetite Nanoparticles / Q000633:toxicity*; D008297:Male; D018675:Toxicity Tests
chemical_list: D058185:Magnetite Nanoparticles
keywords: Controlled release; Fe3O4; cochlea; implant; local drug delivery