A Benchtop Round Window Model for Studying Magnetic Nanoparticle Transport to the Inner Ear

Mukund M. Goyal, Sarek A. Shen, Mohamed Lehar, Angela Martinez, Hakim Hiel, Canhui Wang, Yulin Liu, Chao Wang, Daniel Q. Sun

Research output: Contribution to journalArticlepeer-review

Abstract

Introduction: The round window membrane (RWM) presents a significant barrier to the local application of therapeutics to the inner ear. We demonstrate a benchtop preclinical RWM model and evaluate superparamagnetic iron oxide nanoparticles (SPIONs) as vehicles for magnetically assisted drug delivery. Methods: Guinea pig RWM explants were inset into a 3D-printed dual chamber benchtop device. Custom-synthesized 7-nm iron core nanoparticles were modified with different polyethylene glycol chains to yield two sizes of SPIONs (NP-PEG600 and NP-PEG3000) and applied to the benchtop model with and without a magnetic field. Histologic analysis of the RWM was performed using transmission electron microscopy (TEM) and confocal microscopy. Results: Over a 4-h period, 19.5 ± 1.9% of NP-PEG3000 and 14.6 ± 1.9% of NP-PEG600 were transported across the guinea pig RWM. The overall transport increased by 1.45× to 28.4 ± 5.8% and 21.0 ± 2.0%, respectively, when a magnetic field was applied. Paraformaldehyde fixation of the RWM decreased transport significantly (NP-PEG3000: 7.6 ± 1.5%; NP-PEG600: 7.0 ± 1.6%). Confocal and electron microscopy analysis demonstrated nanoparticle localization throughout all cellular layers and layer-specific transport characteristics within RWM. Conclusion: The guinea pig RWM explant benchtop model allows for targeted and practical investigations of transmembrane transport in the development of nanoparticle drug delivery vehicles. The presence of a magnetic field increases SPION delivery by 45%–50% in a nanoparticle size- and cellular layer-dependent manner. Level of Evidence: NA Laryngoscope, 134:3355–3362, 2024.

Original languageEnglish (US)
Pages (from-to)3355-3362
Number of pages8
JournalLaryngoscope
Volume134
Issue number7
DOIs
StatePublished - Jul 2024

Keywords

  • drug delivery
  • ex vivo model
  • hearing loss
  • intratympanic delivery
  • nanoparticle transport
  • round window membrane
  • super-paramagnetic iron oxide nanoparticles

ASJC Scopus subject areas

  • Otorhinolaryngology

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