Junctional Modulation of Round Window Membrane Enhances Dexamethasone Uptake into the Inner Ear and Recovery after NIHL

Delivery of substances into the inner ear via local routes is increasingly being used in clinical treatment. Studies have focused on methods to increase permeability through the round window membrane (RWM) and enhance drug diffusion into the inner ear. However, the clinical applications of those methods have been unclear and few studies have investigated the efficacy of methods in an inner ear injury model. Here, we employed the medium chain fatty acid caprate, a biologically safe, clinically applicable substance, to modulate tight junctions of the RWM. Intratympanic treatment of sodium caprate (SC) induced transient, but wider, gaps in intercellular spaces of the RWM epithelial layer and enhanced the perilymph and cochlear concentrations/uptake of dexamethasone. Importantly, dexamethasone co–administered with SC led to significantly more rapid recovery from noise–induced hearing loss at 4 and 8 kHz, compared with the dexamethasone-only group. Taken together, our data indicate that junctional modulation of the RWM by SC enhances dexamethasone uptake into the inner ear, thereby hastening the recovery of hearing sensitivity after noise trauma.

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Cutaneous and Labyrinthine Tolerance of Bioactive Glass S53P4 in Mastoid and Epitympanic Obliteration Surgery: Prospective Clinical Study

BioMed Research International ◽

10.1155/2015/242319 ◽

2015 ◽

Vol 2015 ◽

pp. 1-6 ◽

Cited By ~ 11

Author(s):

Daniele Bernardeschi ◽

Yann Nguyen ◽

Francesca Yoshie Russo ◽

Isabelle Mosnier ◽

Evelyne Ferrary ◽

...

Keyword(s):

Bioactive Glass ◽

Inner Ear ◽

Round Window ◽

Bone Conduction ◽

Hearing Threshold ◽

Round Window Membrane ◽

Prospective Clinical Study ◽

Local Skin ◽

Local Skin Reaction ◽

Bone Conduction Hearing

Objective. To evaluate the cutaneous and the inner ear tolerance of bioactive glass S53P4 when used in the mastoid and epitympanic obliteration for chronic otitis surgery.Material and Methods. Forty-one cases have been included in this prospective study. Cutaneous tolerance was clinically evaluated 1 week, 1 month, and 3 months after surgery with a physical examination of the retroauricular and external auditory canal (EAC) skin and the presence of otalgia; the inner ear tolerance was assessed by bone-conduction hearing threshold 1 day after surgery and by the presence of vertigo or imbalance.Results. All surgeries but 1 were uneventful: all patients maintained the preoperative bone-conduction hearing threshold except for one case in which the round window membrane was opened during the dissection of the cholesteatoma in the hypotympanum and this led to a dead ear. No dizziness or vertigo was reported. Three months after surgery, healing was achieved in all cases with a healthy painless skin. No cases of revision surgery for removal of the granules occurred in this study.Conclusion. The bioactive glass S53P4 is a well-tolerated biomaterial for primary or revision chronic otitis surgery, as shown by the local skin reaction which lasted less than 3 months and by the absence of labyrinthine complications.

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Inner Ear Pathology and Otitis Media

Annals of Otology Rhinology & Laryngology ◽

10.1177/00034894800890s358 ◽

1980 ◽

Vol 89 (3_suppl) ◽

pp. 249-253 ◽

Cited By ~ 34

Author(s):

Michael M. Paparella ◽

Marcos V. Goycoolea ◽

William L. Meyerhoff

Keyword(s):

Inner Ear ◽

Otitis Media ◽

Round Window ◽

Round Window Membrane

Insidious inner ear complications of otitis media have been and are being studied in our laboratory. The purpose of this paper is to review these studies, coordinate, capsulize and highlight the results with emphasis on the transport role of the round window membrane.

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Eradicating Otomycosis with Terbinafine Solution: Basic and Clinical Investigation

Audiology and Neurotology ◽

10.1159/000501540 ◽

2019 ◽

Vol 24 (4) ◽

pp. 183-190

Author(s):

Ting-Hua Yang ◽

Yi-Ho Young

Keyword(s):

Clinical Practice ◽

Inner Ear ◽

Morphological Study ◽

Antifungal Agents ◽

Clinical Investigation ◽

Round Window ◽

Round Window Membrane ◽

Potential Candidate ◽

Potential Treatment ◽

Total Dosage

Background: Otomycosis still remains intractable in clinical practice, likely because topical antifungal agents lack efficacy or are potentially toxic to the inner ear end organs. Objectives: The aim of this study was to investigate whether terbinafine solution is a potential candidate for treating intractable otomycosis in humans. In addition, the toxic effect on the inner ear was also assessed by animal models treated with terbinafine. Methods: Guinea pigs were instilled with 0.1 mL terbinafine (10 and 25 mg/mL) in the left round window membrane. At 2 weeks after treatment, all animals underwent an inner ear test battery and were then sacrificed for morphological study. Clinically, 20 patients with otomycosis were treated with terbinafine solution at a dosage of 0.4 mg. Results: All terbinafine-treated animals showed intact inner ear function when total dosage of terbinafine was <2.5 mg, which was further confirmed by morphological study. Subsidence of otomycosis was achieved in all 20 patients 1 week after treatment with terbinafine (0.4 mg) without untoward effect. No evidence of recurrence was noted 1 year after treatment. Conclusion: The paucity of inner ear toxicity of terbinafine even at a dosage of 2.5 mg was identified in guinea pig models morphologically and physiologically. Topical application of terbinafine solution at a dosage of 0.4 mg may be a potential treatment for otomycosis in humans.

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Intratympanic Steroid Treatment of Inner Ear Disease and Tinnitus (Preliminary Report)

Ear Nose & Throat Journal ◽

10.1177/014556139607500806 ◽

1996 ◽

Vol 75 (8) ◽

pp. 468-488 ◽

Cited By ~ 127

Author(s):

Herbert Silverstein ◽

Daniel Choo ◽

Seth I. Rosenberg ◽

Jeffery Kuhn ◽

Michael Seidman ◽

...

Keyword(s):

Inner Ear ◽

Round Window ◽

Meniere’S Disease ◽

Menière’S Disease ◽

Round Window Membrane ◽

Meniere's Disease ◽

Ménière’S Disease ◽

Menière's Disease ◽

Inner Ear Disease ◽

Ménière's Disease

Intratympanic instillation of Depo-Medrol® (80 mg/cc), dexamethasone ophthalmic solution (1 mg/cc), or dexamethasone intravenous (4 mg/cc) solution produces improvement of cochlear function in certain patients with Meniere's disease, autoimmune inner ear disease and sudden sensorineural deafness. Tinnitus improved in 47%, most often in patients with Meniere's disease (9 of 15; 60%). The SRT improvement of greater than 10 dB or SD greater than 15% was documented in 41% (average improvement in SRT: 15 dB; SD: 24%). Patients with tinnitus and bilateral sensorineural hearing loss (i.e., presbycusis) did not benefit from the treatment. Prior to treatment with intratympanic medication, laser-assisted tympanostomy with middle ear exploration, using otoendoscopy to determine the status of the round window niche and remove mucosal folds, helps in making the round window membrane accessible to local application of drops. Placing Gelfoam into the round window niche under direct vision, and using a Venturi Bobbin tube in the tympanic membrane, appears to be a satisfactory method for delivering medication to the inner ear fluids. The medication can be injected by the physician through the tube into the middle ear, or the patient can perform self-treatment at home, placing medication in the external auditory canal. A double-blind, cross-over study in patients with Meniere's disease is now in progress with Institutional Review Board (IRB) approval, which will be reported at a later date. This preliminary study has shown that intratympanic steroids may affect the symptoms of hearing loss and tinnitus in patients with various inner ear problems. Patients with Meniere's disease appear to respond in the highest percentage of cases. Hopefully, additional research will suggest the appropriate drugs which can be used to treat inner ear disease. Direct application of the drug to the round window membrane may increase the concentration in the inner ear fluids, thus avoiding the systemic effects.

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Inner ear biocompatibility of lipid nanocapsules after round window membrane application

International Journal of Pharmaceutics ◽

10.1016/j.ijpharm.2010.11.006 ◽

2011 ◽

Vol 404 (1-2) ◽

pp. 211-219 ◽

Cited By ~ 32

Author(s):

Ya Zhang ◽

Weikai Zhang ◽

Marian Löbler ◽

Klaus-Peter Schmitz ◽

Patrick Saulnier ◽

...

Keyword(s):

Inner Ear ◽

Round Window ◽

Round Window Membrane ◽

Lipid Nanocapsules

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Effect of oxygen-flooding to the round window membrane on the inner ear function of the anoxic cochlea.

Practica Oto-Rhino-Laryngologica ◽

10.5631/jibirin.79.1143 ◽

1986 ◽

Vol 79 (7) ◽

pp. 1143-1147

Author(s):

Toshimitsu KOBAYASHI ◽

Takuji OKITSU ◽

Katsuhisa IKEDA ◽

Jun KUSAKARI

Keyword(s):

Inner Ear ◽

Round Window ◽

Round Window Membrane ◽

Effect Of Oxygen

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Rupture of the Round Window Membrane in Inner Ear Barotrauma

Archives of Otolaryngology - Head and Neck Surgery ◽

10.1001/archotol.1974.00780030451010 ◽

1974 ◽

Vol 99 (6) ◽

pp. 437-442 ◽

Cited By ~ 26

Author(s):

P. Freeman ◽

J. Tonkin ◽

C. Edmonds

Keyword(s):

Inner Ear ◽

Round Window ◽

Round Window Membrane ◽

Inner Ear Barotrauma

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Spontaneous Remission in Experimental Autoimmune Labyrinthitis

Annals of Otology Rhinology & Laryngology ◽

10.1177/000348949210101208 ◽

1992 ◽

Vol 101 (12) ◽

pp. 1007-1014 ◽

Cited By ~ 18

Author(s):

Shigeharu Yamanobe ◽

Jeffrey P. Harris

Keyword(s):

Inner Ear ◽

Time Course ◽

Round Window ◽

Spontaneous Remission ◽

Intradermal Injection ◽

Round Window Membrane ◽

Cellular Infiltration ◽

Auditory Brain Stem Response ◽

Hearing Thresholds ◽

Experimental Autoimmune

We investigated the time course of hearing impairment and cellular infiltration into the inner ear after systemic sensitization of guinea Pigs with a single intradermal injection of bovine inner ear antigen (IEAg) in complete Freund's adjuvant (CFA). Lymphocytes and polymorphonucleocytes appeared mainly in the scala tympani on days 7 to 14, and in addition there was thickening and cellular infiltration of the round window membrane at day 14. These cellular infiltrations resolved after day 28. The auditory brain stem response thresholds from IEAg-sensitized animals were significantly elevated after day 7. Some sensitized animals (n = 5) had spontaneous remissions after day 28; however, the hearing thresholds did not completely recover. These results demonstrate that experimental autoimmune labyrinthitis can be induced by a single inoculation of IEAg-CFA and that remission, as evidenced by clearing of the cochlear cellular infiltration and improved hearing thresholds, can occur spontaneously.

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

10.21203/rs.3.rs-915620/v1 ◽

2021 ◽

Author(s):

So-Young Jung ◽

Zion Kang ◽

Soonmin Kwon ◽

Juhye Lee ◽

Subin Kim ◽

...

Keyword(s):

Hearing Loss ◽

Inner Ear ◽

Round Window ◽

Round Window Membrane ◽

In Vivo Test ◽

Drug Concentrations ◽

Intratympanic Injection ◽

Acute Hearing Loss

Abstract 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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