Superparamagnetic Nanoparticle Delivery to the Cochlea Through Round Window by External Magnetic Field: Feasibility and Toxicity

Abstract

Introduction. The objective of this study was to evaluate the feasibility and toxicity of superparamagnetic iron oxide nanoparticles (SPIONs) administered into the cochlea through the round window (RW) by an external magnetic field. Materials and Methods. In 5 Wistar rats, the left RW was punctured. SPIONs suspended in hyaluronic gel (5 mg/mL) were applied in the RW niche and covered by a muscle graft. The nanoparticles were mobilized using a rare earth magnet (0.54 T) held in 4 consecutive positions around the head. The right ear served as control. Hearing function was monitored by auditory brainstem responses (4-32 kHz tone bursts). Results. The auditory thresholds remained unchanged 1 month after the administration. The histological study of the cochleae showed that SPIONs were driven into the scala tympani in the basal turn, the second turn, and the apex. Conclusion. Superparamagnetic nanoparticles can be driven inside the cochlea toward the apex with a preserved hearing up to 1 month in rats.

Use of Super Paramagnetic Iron Oxide Nanoparticles as Drug Carriers in Brain and Ear: State of the Art and Challenges

“…More importantly, SPIONs can represent an efficient means of drug delivery as we will develop in this review [39,40]. SPIONs are particularly interesting for drug delivery in CNS and inner ear since both structures are guarded by a blood-organ barrier, contain deep-seated, functionally sensitive, and fragile structures [41], and can benefit from targeted deliveries using an external magnetic field (EMF) [42][43][44][45]. Modifying their surface charge, combining them to hydrophile molecules (e.g., Polyethylene Glycol, PEG; Polyethylenimine, PEI; Polylactic-co-glycolic acid, PGLA) [40,46] or coupling them to antibodies (transferrin receptor antibodies or lactoferrin) [47,48] can further facilitate their diffusion through BBB [49,50].…”

“…In order to reach the inner ear, SPIONs could be driven by an EMF though the round window [45,79], using a cochleostomy [44] or deposited in the middle ear for passive diffusion through the round window [111]. In vitro, an EMF was used to increase the migration of SPIONs in cochlear cells [62,96].…”

“…The route of choice in most studies targeting CNS is the IV injection [42,43,48,57,76,78,90]. For the inner ear, intratympanic injection is preferred since it has the advantage of delivering a large SPION quantity by a minimally invasive route [44,45,79].…”

Beyond Oncological Hyperthermia: Physically Drivable Magnetic Nanobubbles as Novel Multipurpose Theranostic Carriers in the Central Nervous System

“…B-mode cineloops (60 sec) were acquired and recorded for postproduction both in the absence and in the presence of the permanent magnet exerting a magnetic force in the direction of injection (see Figure 6b). Snapshots from cineloops were extracted at different time frames (5,15,25, 55 sec) after the initial injection and compared in the different conditions.…”

“…As a matter of fact, magnetic nanoparticles have already been proposed to bypass the Blood–Brain Barrier (BBB) to treat glioblastomas and neurodegenerative diseases [ 8 , 9 , 10 , 11 , 12 ] as well as in regenerative medicine [ 13 , 14 ] and drug delivery [ 15 , 16 ]. Very recently magnetic nanoparticles have been proposed as transducers in advanced neuromodulation, via the hysteretic heat when exposed to alternated magnetic fields [ 17 ].…”