Long term in vivo release profile of dexamethasone loaded silicone rods implanted into the cochlea of guinea pigs

Liebau, Arne; Kammerer, Bernd; Kather, Michel; Schilp, S; Mugridge, Kenneth G.; Tillein, Jochen; Braun, Susanne; Plontke, Stefan K.

doi:10.1055/s-0039-1686442

Cited by 3 publications

(3 citation statements)

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“…Unfortunately, however, there are few methods to accurately measure dexamethasone concentrations in cochlear tissue. In this study, the concentration of dexamethasone in cochlear homogenate was evaluated by LC/MS in the manner described by Liebau et al (25). For an accurate comparison between animals, the amount of dexamethasone was quanti ed based on the amount of protein in cochlear homogenate, and surprisingly, at 6 h after drug injection, NUFS B produced a tissue drug concentration approximately 26 times the concentration achieved by Dex-SP.…”

Section: Discussionmentioning

confidence: 99%

“…In order to determine the concentration of dexamethasone absorbed into the tissues of the cochlea, the concentration of dexamethasone in cochlear homogenate was analyzed by LC/MS (25). The cochlea was harvested from animals, then immersed in isotonic phosphate buffered saline (PBS) and washed to remove any drug residue from the outside of the cochlea.…”

Section: Preparation Of Cochlear Homogenates and Measurement Of Dexamethasone Concentrationsmentioning

confidence: 99%

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Efficiency of a Dexamethasone Nanosuspension as an Intratympanic Injection for Acute Hearing Loss

Jung

Kang

Kwon

et al. 2021

Preprint

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Background: Dexamethasone sodium phosphate (Dex-SP) is the most commonly used drug for intratympanic injection in acute hearing loss, but its penetration efficiency into the inner ear is very low. To address this problem, we evaluated the possibility of dexamethasone nanosuspensions as intratympanic injection because the lipophilicity of drugs can affect their permeation of the round window membrane, an important pathway from the middle ear to the cochlea.Results: Three types of dexamethasone nanosuspensions were prepared; the dexamethasone nanocrystals in the three nanosuspensions were between approximately 250 and 350 nm in size. In order to compare the efficiency of Dex-SP and a dexamethasone nanosuspension in delivering dexamethasone to the inner ear, the concentrations of dexamethasone in perilymph and cochlear tissues were compared by liquid chromatography–mass spectrometry. The dexamethasone nanosuspensions showed significantly higher drug concentrations in perilymph and cochlear tissue than Dex-SP at 6 h; interestingly, animals treated with a nanosuspension showed a 26-fold higher dexamethasone concentration in the cochlear tissue than the Dex-SP group. In addition, the dexamethasone nanosuspension achieved better glucocorticoid receptor phosphorylation than Dex-SP both in vitro and in vivo, and in the ototoxic animal model, it showed a significantly better hearing protective effect than Dex-SP against ototoxic drugs. In safety evaluation, the nanosuspension showed no toxicity at concentrations up to 20 mg/mL in an in vivo test.Conclusions: A nanosuspension of dexamethasone was able to deliver dexamethasone to the cochlea very safely and efficiently and showed potential as a formula for intratympanic injection. In addition, it can be applied in studies on the delivery of various hydrophobic antioxidants to treat acute hearing loss.

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Section: Discussionmentioning

confidence: 99%

Section: Preparation Of Cochlear Homogenates and Measurement Of Dexamethasone Concentrationsmentioning

confidence: 99%

Efficiency of a Dexamethasone Nanosuspension as an Intratympanic Injection for Acute Hearing Loss

Jung

Kang

Kwon

et al. 2021

Preprint

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“…Coatings on cochlear implants represent a delivery modality that is easily integrated with research and clinical devices. There continues to be significant work characterizing the release kinetics with the objective of achieving stable and sustained concentration profiles within ST. A simulated CI device consisting of DEX loaded silicon rods, with DEX concentrations of 0.1%, 1%, and 10%, was tested via implantation in ST of guinea pigs with perilymph sampling up to 7 weeks post-implantation [32]. Sustained concentrations of about 60 and 100 ng/mL were observed in the perilymph for the 1 and 10% loaded rods respectively, demonstrating the potential for therapeutic dosing by loading of DEX into the silicone of a CI electrode array.…”

Section: Steroid Elution Coatingsmentioning

confidence: 99%

Microtechnologies for inner ear drug delivery

Forouzandeh

Borkholder²

2020

Current Opinion in Otolaryngology &Amp; Head &Amp; Neck Surgery

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Purpose of review-Treatment of auditory dysfunction is dependent on inner ear drug delivery, with microtechnologies playing an increasingly important role in cochlear access and pharmacokinetic profile control. This review examines recent developments in the field relevant to both clinical and animal research environments.Recent findings-Micropump technologies are being developed that provide dynamic control of flow rates with refillable reservoirs to enable timed delivery of a series of multiple agents for protection or regeneration therapies. These micropumps can be combined with cochlear implants with integral catheters or used independently with cochleostomy or RWM delivery modalities for therapy development in animal models. Sustained release of steroids with coated cochlear implants remains an active area of research with first-time-in-human demonstration of reduced electrode impedances. Advanced coatings containing neurotrophin producing cells have enhanced spiral ganglion neuron survival in animal models, and have proven safe in a human study. Microneedles have emerged as a novel method for controlled microperforation of the round window membrane with significant enhancement in permeability, which can be combined with emerging matrix formulations that optimize biological interaction and drug release kinetics.Summary-Microsystem technologies and associated fabrication techniques are providing enhanced and more controlled access to the inner ear for advanced drug delivery approaches, alone and in conjunction with cochlear implants.

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

Lehner

Menzel

Gündel

et al. 2021

Drug Deliv. and Transl. Res.

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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

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Long term in vivo release profile of dexamethasone loaded silicone rods implanted into the cochlea of guinea pigs

Cited by 3 publications

References 0 publications

Efficiency of a Dexamethasone Nanosuspension as an Intratympanic Injection for Acute Hearing Loss

Efficiency of a Dexamethasone Nanosuspension as an Intratympanic Injection for Acute Hearing Loss

Microtechnologies for inner ear drug delivery

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

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