Microimaging of a novel intracochlear drug delivery device in combination with cochlear implants in the human inner ear

Abstract

The effective delivery of drugs to the inner ear is still an unmet medical need. Local controlled drug delivery to this sensory organ is challenging due to its location in the petrous bone, small volume, tight barriers, and high vulnerability. Local intracochlear delivery of drugs would overcome the limitations of intratympanic (extracochlear) and systemic drug application. The requirements for such a delivery system include small size, appropriate flexibility, and biodegradability. We have developed biodegradable PLGA-based implants for controlled intracochlear drug release that can also be used in combination with cochlear implants (CIs), which are implantable neurosensory prosthesis for hearing rehabilitation. The drug carrier system was tested for implantation in the human inner ear in 11 human temporal bones. In five of the temporal bones, CI arrays from different manufacturers were implanted before insertion of the biodegradable PLGA implants. The drug carrier system and CI arrays were implanted into the scala tympani through the round window. Implanted temporal bones were evaluated by ultra-high-resolution computed tomography (µ-CT) to illustrate the position of implanted electrode carriers and the drug carrier system. The µ-CT measurements revealed the feasibility of implanting the PLGA implants into the scala tympani of the human inner ear and co-administration of the biodegradable PLGA implant with a CI array. Graphical abstract

Safety and audiological outcome in a case series of tertiary therapy of sudden hearing loss with a biodegradable drug delivery implant for controlled release of dexamethasone to the inner ear

“…In addition, information is missing if residual solvents are remaining in the implants due to the manufacturing process. Lehner et al developed a PLGA based drug depot with an improved, homogenous drug release profile over more than 5 weeks and smoother material characteristic which has already been tested in human temporal bones ( Lehner et al, 2019 , 2022 ). In PLGA-based implants, including Ozurdex ® , the free acids emerging during degradation can change the pH microclimate inside and around the implant ( Siepmann et al, 2005 ; Schädlich et al, 2014 ).…”

“…A drug delivery system separated from the electrode array is desirable because both systems can be optimized independently. This creates new opportunities to personalized medicines as suggested previously (Plontke et al, 2017;Lehner et al, 2022). Although the intracochlear application of drugs is likely associated with higher risks than intratympanic application (Salt and Plontke, 2009) the above studies on intracochlear glucocorticoid drug application did not report relevant side effects.…”

“…For intravitreal application, the rod-shaped implant is injected from a pen-like device consisting of a hollow stainless-steel needle in a disposable applicator. For the adopted local controlled release drug delivery to the inner ear, the implant was removed from its applicator and cut into pieces of approximately 0.8–1.5 mm length, according to the size of the human RW niche (1.55 mm [range: 0.8–1.6 mm] or 1.65 mm [range: 0.96–2.28 mm] by 1.2 mm [range: 0.8–1.6 mm] ( Su et al, 1982 ; Lang and Kothe, 1987 ; Figures 1D–F ) and for implantation into scala tympani according to a recent study investigating feasible implant dimensions for intracochlear drug delivery in the human ( Lehner et al, 2022 ).…”

Biological Response Dynamics to Cochlear Implantation: Modeling and Modulating the Electrode–Tissue Interface

“…Dexamethasone eluting electrodes are already being assessed in preclinical (Stathopoulos et al 2014; Douchement et al 2015; Bas et al 2016; Plontke et al 2017) and clinical settings (Briggs et al 2020). Also, the are undergoing developments of external biodegradable carrier systems for controlled intracochlear drug release that can be used in combination with CIs (Lehner et al 2021). Furthermore, localized therapeutic hypothermia may significantly reduce the traumatic effects of electrode insertion and improve conservation of residual hearing (Tamames et al 2016; Perez et al 2019).…”

An Overview of Nanoparticle Drug Delivery for Ototoxin and Noise Mediated Hearing Loss Treatment

“…166 systemic administration route (Oral, intravenous and intramural) are predominantly used clinical method to treat some type of ear disorder, despite it has low therapeutic carriage ability and related hostile effects due to inadequate blood supply in the inner ear's and the insufficient dispersion of the blood-inner ear barrier (BLB). 35,[65][66][67][68] Intracochlear route thru cochleostomy seems to be the most implicit approach for transporting drug loaded nanoparticles to cochlear tissues, 24,26,[69][70][71] but this is recognized to be more invasive and traumatic to inner ear (Damage the cochlea, worsen or destroy hearing function) than alternative strategies. 68,72,73 Intratympanic (IT) delivery has been manifested to retain higher local drug level in the perilymph as compared to systemic administration due to their dearth of intervention from the blood-labyrinth barrier and systemic reactions.…”