Rationally Designed Magnetic Nanoparticles for Cochlear Drug Delivery: Synthesis, Characterization, and In Vitro Biocompatibility in a Murine Model

Mukund M Goyal; Nancy J Zhou; Philippe F Y Vincent; Elina S Hoffman; Shiv Goel; Chao Wang; Daniel Q Sun

doi:10.1097/ONO.0000000000000013

Rationally Designed Magnetic Nanoparticles for Cochlear Drug Delivery: Synthesis, Characterization, and In Vitro Biocompatibility in a Murine Model

Otol Neurotol Open. 2022 Jul 20;2(3):e013. doi: 10.1097/ONO.0000000000000013. eCollection 2022 Sep.

Authors

Mukund M Goyal¹, Nancy J Zhou², Philippe F Y Vincent³, Elina S Hoffman¹, Shiv Goel¹, Chao Wang¹, Daniel Q Sun³

Affiliations

¹ Department of Chemical and Biomolecular Engineering, Johns Hopkins University, Baltimore, MD.
² School of Medicine, Johns Hopkins University, Baltimore, MD.
³ Department of Otolaryngology - Head and Neck Surgery, Johns Hopkins University, Baltimore, MD.

Abstract

Hypothesis: Magnetic nanoparticles (MNPs) for cochlear drug delivery can be precisely engineered for biocompatibility in the cochlea.

Background: MNPs are promising drug delivery vehicles that can enhance the penetration of both small and macromolecular therapeutics into the cochlea. However, concerns exist regarding the application of oxidative, metal-based nanomaterials to delicate sensory tissues of the inner ear. Translational development of MNPs for cochlear drug deliver requires specifically tuned nanoparticles that are not cytotoxic to inner ear tissues. We describe the synthesis and characterization of precisely tuned MNP vehicles, and their in vitro biocompatibility in murine organ of Corti organotypic cultures.

Methods: MNPs were synthesized via 2-phase ligand transfer process with precise control of nanoparticle size. Core and hydrodynamic sizes of nanoparticles were characterized using electron microscopy and dynamic light scattering, respectively. In vitro biocompatibility was assayed via mouse organ of Corti organotypic cultures with and without an external magnetic field gradient. Imaging was performed using immunohistochemical labeling and confocal microscopy. Outer hair cell, inner hair cell, and spiral ganglion neurites were individually quantified.

Results: Monocore PEG-MNPs of 45 and 148 nm (mean hydrodynamic diameter) were synthesized. Organ of Corti cultures demonstrated preserved outer hair cell, inner hair cell, and neurite counts across 2 MNP sizes and doses, and irrespective of external magnetic field gradient.

Conclusion: MNPs can be custom-synthesized with precise coating, size, and charge properties specific for cochlear drug delivery while also demonstrating biocompatibility in vitro.

Keywords: Biocompatibility; Drug delivery; Magnetic nanoparticles; Organ of Corti.