Long-Term in vivo Release Profile of Dexamethasone-Loaded Silicone Rods Implanted Into the Cochlea of Guinea Pigs

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

doi:10.3389/fneur.2019.01377

Cited by 19 publications

(9 citation statements)

References 71 publications

(97 reference statements)

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“…The authors highlighted that silicone is a more suitable matrix for drug release at the oval window than resorbable biopolymers (such as PLGA or gelatine), as a higher drug load and a prolonged release can be achieved, which is favorable for chronic treatment. Additionally, several research groups have investigated the DEX release from silicone cochlear implants [25,[38][39][40][41], all showing a burst followed by a prolonged release as also shown for our EECI. Liebau et al observed silicone rods loaded with 0.1, 1, and 10% DEX after implantation into the cochlea of guinea pigs [31].…”

Section: Drug Releasementioning

confidence: 55%

Individualized, Additively Manufactured Drug-Releasing External Ear Canal Implant for Prevention of Postoperative Restenosis: Development, In Vitro Testing, and Proof of Concept in an Individual Curative Trial

et al. 2022

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Postoperative restenosis in patients with external ear canal (EEC) atresia or stenosis is a common complication following canaloplasty. Our aim in this study was to explore the feasibility of using a three dimensionally (3D)-printed, patient-individualized, drug ((dexamethasone (DEX)), and ciprofloxacin (cipro))-releasing external ear canal implant (EECI) as a postoperative stent after canaloplasty. We designed and pre-clinically tested this novel implant for drug release (by high-performance liquid chromatography), biocompatibility (by the MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay), bio-efficacy (by the TNF-α (tumor necrosis factor-alpha)-reduction test (DEX) and inhibition zone test (for cipro)), and microbial contamination (formation of turbidity or sediments in culture medium). The EECI was implanted for the first time to one patient with a history of congenital EEC atresia and state after three canaloplasties due to EEC restenosis. The preclinical tests revealed no cytotoxic effect of the used materials; an antibacterial effect was verified against the bacteria Staphylococcus aureus and Pseudomonas aeruginosa, and the tested UV-irradiated EECI showed no microbiological contamination. Based on the test results, the combination of silicone with 1% DEX and 0.3% cipro was chosen to treat the patient. The EECI was implantable into the EEC; the postoperative follow-up visits revealed no otogenic symptoms or infections and the EECI was explanted three months postoperatively. Even at 12 months postoperatively, the EEC showed good epithelialization and patency. Here, we report the first ever clinical application of an individualized, drug-releasing, mechanically flexible implant and suggest that our novel EECI represents a safe and effective method for postoperatively stenting the reconstructed EEC.

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Section: Drug Releasementioning

confidence: 55%

Individualized, Additively Manufactured Drug-Releasing External Ear Canal Implant for Prevention of Postoperative Restenosis: Development, In Vitro Testing, and Proof of Concept in an Individual Curative Trial

et al. 2022

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“…In this study, the concentration of dexamethasone in cochlear homogenate was evaluated by LC/MS in the manner described by Liebau et al. ( 2019 ). For an accurate comparison between animals, the amount of dexamethasone was quantified 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 (Liebau et al., 2019 ). 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: Methodsmentioning

confidence: 99%

Efficiency of a dexamethasone nanosuspension as an intratympanic injection for acute hearing loss

et al. 2021

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Dexamethasone sodium phosphate (Dex-SP) is the most commonly used drug administered via intratympanic injection for the treatment of acute hearing loss, but its penetration efficiency into the inner ear is very low. To address this problem, we evaluated the possibility of administering dexamethasone nanosuspensions via intratympanic injection because hydrophobic drugs might be more effective in penetrating the inner ear. Three types of dexamethasone nanosuspensions were prepared; the dexamethasone nanoparticles in the three nanosuspensions were between approximately 250 and 350 nm in size. To compare the efficiency of Dex-SP and 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 resulted in significantly higher drug concentrations in perilymph and cochlear tissues than Dex-SP at 6 h; interestingly, animals treated with nanosuspensions showed a 26-fold higher dexamethasone concentrations in their cochlear tissues than animals treated with Dex-SP. In addition, dexamethasone nanosuspension caused better glucocorticoid receptor phosphorylation than Dex-SP both in vitro and in vivo , and in the ototoxic animal model, the nanosuspension showed a significantly better hearing-protective effect against ototoxic drugs than Dex-SP. In the in vivo safety evaluation, the nanosuspension showed no toxicity at concentrations up to 20 mg/mL. In conclusion, 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.

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“…Glucocorticosteroids were intensively studied to reduce EIT and DEX-eluting electrodes, resulting in a considerable amount of research data [85][86][87][88][89][90]. In an animal model, Douchement et al used electrodes embedded in a silicone matrix loaded with various concentrations of DEX and compared them to simple electrodes, evaluating the hearing thresholds at 4-6 weeks after surgery and one year after surgery.…”

Section: Drug-eluting Electrodesmentioning

confidence: 99%

Current Concepts and Future Trends in Increasing the Benefits of Cochlear Implantation: A Narrative Review

et al. 2022

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Hearing loss is the most common neurosensory disorder, and with the constant increase in etiological factors, combined with early detection protocols, numbers will continue to rise. Cochlear implantation has become the gold standard for patients with severe hearing loss, and interest has shifted from implantation principles to the preservation of residual hearing following the procedure itself. As the audiological criteria for cochlear implant eligibility have expanded to include patients with good residual hearing, more attention is focused on complementary development of otoprotective agents, electrode design, and surgical approaches. The focus of this review is current aspects of preserving residual hearing through a summary of recent trends regarding surgical and pharmacological fundamentals. Subsequently, the assessment of new pharmacological options, novel bioactive molecules (neurotrophins, growth factors, etc.), nanoparticles, stem cells, and gene therapy are discussed.

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Long-Term in vivo Release Profile of Dexamethasone-Loaded Silicone Rods Implanted Into the Cochlea of Guinea Pigs

Cited by 19 publications

References 71 publications

Individualized, Additively Manufactured Drug-Releasing External Ear Canal Implant for Prevention of Postoperative Restenosis: Development, In Vitro Testing, and Proof of Concept in an Individual Curative Trial

Individualized, Additively Manufactured Drug-Releasing External Ear Canal Implant for Prevention of Postoperative Restenosis: Development, In Vitro Testing, and Proof of Concept in an Individual Curative Trial

Efficiency of a dexamethasone nanosuspension as an intratympanic injection for acute hearing loss

Current Concepts and Future Trends in Increasing the Benefits of Cochlear Implantation: A Narrative Review

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