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

doi:10.1002/lary.31345

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

Laryngoscope. 2024 Feb 20. doi: 10.1002/lary.31345. Online ahead of print.

Authors

Mukund M Goyal¹, Sarek A Shen², Mohamed Lehar², Angela Martinez², Hakim Hiel², Canhui Wang¹, Yulin Liu¹, Chao Wang², Daniel Q Sun^{1

3}

Affiliations

¹ Department of Chemical & Biomolecular Engineering, Johns Hopkins University, Baltimore, Maryland, USA.
² Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
³ Department of Otolaryngology-Head and Neck Surgery, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA.

PMID: 38379206
DOI: 10.1002/lary.31345

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, 2024.

Keywords: drug delivery; ex vivo model; hearing loss; intratympanic delivery; nanoparticle transport; round window membrane; super-paramagnetic iron oxide nanoparticles.

Abstract

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