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 language | English (US) |
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Pages (from-to) | 3355-3362 |
Number of pages | 8 |
Journal | Laryngoscope |
Volume | 134 |
Issue number | 7 |
DOIs | |
State | Published - 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