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

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.

scholarly journals Elucidation of the Hdac2/Sp1/miR-204-5p/Bcl-2 axis as a modulator of cochlear apoptosis via in vivo/in vitro models of acute hearing loss

2021 ◽  
Vol 23 ◽  
pp. 1093-1109
Author(s):  
Lisheng Xie ◽  
Qiongqiong Zhou ◽  
Xiaorui Chen ◽  
Xiaoping Du ◽  
Zhibiao Liu ◽  
...  
Keyword(s):  
Hearing Loss ◽  
In Vitro Models ◽  
Acute Hearing Loss

scholarly journals A Window of Opportunity: Perilymph Sampling from the Round Window Membrane Can Advance Inner Ear Diagnostics and Therapeutics

2022 ◽  
Vol 11 (2) ◽  
pp. 316
Author(s):  
Madeleine St. Peter ◽  
Athanasia Warnecke ◽  
Hinrich Staecker
Keyword(s):  
Hearing Loss ◽  
Sensorineural Hearing Loss ◽  
Inner Ear ◽  
Hearing Aids ◽  
Biomarker Discovery ◽  
Treatment Options ◽  
Round Window ◽  
Sensorineural Hearing ◽  
Round Window Membrane ◽  
Promising Source

In the clinical setting, the pathophysiology of sensorineural hearing loss is poorly defined and there are currently no diagnostic tests available to differentiate between subtypes. This often leaves patients with generalized treatment options such as steroids, hearing aids, or cochlear implantation. The gold standard for localizing disease is direct biopsy or imaging of the affected tissue; however, the inaccessibility and fragility of the cochlea make these techniques difficult. Thus, the establishment of an indirect biopsy, a sampling of inner fluids, is needed to advance inner ear diagnostics and allow for the development of novel therapeutics for inner ear disease. A promising source is perilymph, an inner ear liquid that bathes multiple structures critical to sound transduction. Intraoperative perilymph sampling via the round window membrane of the cochlea has been successfully used to profile the proteome, metabolome, and transcriptome of the inner ear and is a potential source of biomarker discovery. Despite its potential to provide insight into inner ear pathologies, human perilymph sampling continues to be controversial and is currently performed only in conjunction with a planned procedure where the inner ear is opened. Here, we review the safety of procedures in which the inner ear is opened, highlight studies where perilymph analysis has advanced our knowledge of inner ear diseases, and finally propose that perilymph sampling could be done as a stand-alone procedure, thereby advancing our ability to accurately classify sensorineural hearing loss.

scholarly journals Astaxanthin-loaded polymer-lipid hybrid nanoparticles (ATX-LPN) Assessment of potential otoprotective effects

2019 ◽  
Author(s):  
Jiayi Gu ◽  
Yuming Chen ◽  
Ling Tong ◽  
Xueling Wang ◽  
dehong Yu ◽  
...  
Keyword(s):  
Inner Ear ◽  
Guinea Pigs ◽  
Round Window ◽  
Antioxidant Properties ◽  
Annexin V ◽  
Hybrid Nanoparticles ◽  
Protective Mechanism ◽  
Platinum Based Chemotherapy

Abstract Background: Ototoxicity is one of the major side effects of platinum-based chemotherapy, especially cisplatin therapy. To date, no FDA approved agents to alleviate or prevent this ototoxicity are available. However, ototoxicity is generally believed to be produced by excessive generation of reactive oxygen species (ROS) in the inner ear, thus leading to the development of various antioxidants, which act as otoprotective agents. Astaxanthin (ATX) is an interesting candidate in the development of new therapies for preventing and treating oxidative stress-related pathologies, owing to its unique antioxidant capacity. Methods and Results: In this study, we aimed to evaluate the potential antioxidant properties of ATX in the inner ear by using the HEI-OC1 cell line, zebrafish, and guinea pigs. Because ATX has poor solubility and cannot pass through round window membranes (RWM), we established lipid-polymer hybrid nanoparticles (LPN) for loading ATX. The LPN enabled ATX to penetrate RWM and maintain concentrations in the perilymph in the inner ear for 24 h after a single injection. ATX-LPN were found to have favorable biocompatibility and to strongly affect cisplatin-induced generation of ROS, on the basis of DCFHDA staining in HEI-OC1 cells. JC-1 and MitoTracker Green staining suggested that ATX-LPN successfully reversed the decrease in mitochondrial membrane potential induced by cisplatin in vitro and rescued cells from early stages of apoptosis, as demonstrated by FACS stained with Annexin V-FITC/PI. Moreover, ATX-LPN successfully attenuated OHC losses in cultured organ of Corti and animal models (zebrafish and guinea pigs) in vivo. In investigating the protective mechanism of ATX-LPN, we found that ATX-LPN decreased the expression of pro-apoptotic proteins (caspase 3/9 and cytochrome-c) and increased expression of the anti-apoptotic protein Bcl-2. In addition, the activation of JNK induced by CDDP was up-regulated and then decreased after the administration of ATX-LPN, while P38 stayed unchanged. Conclusions: To best of our knowledge, this is first study concluded that ATX-LPN as a new therapeutic agent for the prevention of cisplatin-induced ototoxicity.

scholarly journals Bacterial Cytolysin Perturbs Round Window Membrane Permeability Barrier In Vivo: Possible Cause of Sensorineural Hearing Loss in Acute Otitis Media

1998 ◽  
Vol 66 (1) ◽  
pp. 343-346 ◽  
Author(s):  
Frank Engel ◽  
Rosemarie Blatz ◽  
Reinhard Schliebs ◽  
Michael Palmer ◽  
Sucharit Bhakdi
Keyword(s):  
Hearing Loss ◽  
Sensorineural Hearing Loss ◽  
Middle Ear ◽  
Round Window ◽  
Acute Otitis Media ◽  
Sensorineural Hearing ◽  
Round Window Membrane ◽  
Permeability Barrier ◽  
Streptolysin O

ABSTRACT The passage of radioiodinated streptolysin-O (SLO) and albumin through the round window membrane (RWM) was studied in vivo. When applied to the middle ear, SLO became quantitatively entrapped in this compartment and no passage to the cochlea occurred. However, flux of radioiodinated albumin through the toxin-damaged RWM was observed. We propose that the passage of noxious macromolecules, such as proteases, from a purulent middle-ear effusion may be facilitated by pore-forming toxins, resulting in cochlear damage and sensorineural hearing loss.

scholarly journals A gyógyszeres kezelésre nem javuló hirtelen halláscsökkenés lépcsőzetes sebészi terápiája

2021 ◽  
Vol 162 (51) ◽  
pp. 2055-2060
Keyword(s):  
Hearing Loss ◽  
Inner Ear ◽  
Hearing Aids ◽  
Cochlear Implantation ◽  
Early Stage ◽  
Round Window ◽  
Complete Recovery ◽  
Round Window Membrane ◽  
Systemic Steroid ◽  
Profound Hearing Loss

Összefoglaló. A hirtelen halláscsökkenés patofiziológiája még nagyrészt tisztázatlan, így oki terápia nem lehetséges. Az elsődleges kezelést a helyileg vagy szisztémásan adott kortikoszteroid jelenti, egységes protokoll azonban nem áll rendelkezésre. Nagy vagy súlyos fokú hirtelen halláscsökkenés esetén kóroki tényezőként felmerül a perilymphafistula lehetősége még azoknál a betegeknél is, akiknél nem szerepel trauma az anamnézisben. A kórkép műtéti kezelése a dobüreg feltárását követően a belső fül ablakainak obliterálása. Amennyiben ez a megoldás nem eredményez megfelelő hallásjavulást, hagyományos vagy implantálható hallókészülékek alkalmazása javasolt. A közleményben részletezett esetünkben teljes siketséggel járó, jobb oldali hirtelen halláscsökkenés alakult ki, melynek hátterében egyértelmű okot azonosítani nem sikerült. Az eredménytelen kombinált, intratympanalis és szisztémás szteroidkezelést követően exploratív tympanotomiát végeztünk, melynek során a belső fül ablakait obliteráltuk. Hallásjavulást ezt követően sem sikerült kimutatni, így cochlearis implantáció elvégzése mellett döntöttünk. Az implantációt a kerek ablakon keresztül végeztük, mely alapján kijelenthetjük, hogy az előzetes kerekablak-obliteráció nem zárja ki a későbbi cochlearis implantációt. Orv Hetil. 2021; 162(51): 2055–2060. Summary. The pathophysiology of sudden sensorineural hearing loss is mainly unknown, therefore no causative treatment exists. Systemic and local administration of corticosteroids serves as first line therapy although protocols vary. In cases of severe or profound hearing loss with no improvement for medical therapy, perilymphatic fistulae can be assumed even without any history of trauma. Therefore, inner ear window obliteration as a primary surgical option in the early stage can be considered. For patients without complete recovery, conventional hearing aids or implantable hearing devices can be offered. In our case report, we present a patient with right sided idiopathic sudden deafness. After failure of conservative combined intratympanic and systemic steroid therapy, explorative tympanotomy and obliteration of the inner ear windows were performed. As no hearing improvement was witnessed, successful cochlear implantation via round window insertion was performed. Our case justifies that obliterating the round window membrane does not rule out further successful cochlear implantation. Orv Hetil. 2021; 162(51): 2055–2060.

scholarly journals Dexamethasone release from photopolymerised PEGDA700 for cochlea drug delivery

2020 ◽  
Vol 6 (3) ◽  
pp. 82-84
Author(s):  
Eickner Thomas ◽  
Michael Teske ◽  
Natalia Rekowska ◽  
Volkmar Senz ◽  
Klaus-Peter Schmitz ◽  
...  
Keyword(s):  
Drug Release ◽  
Round Window ◽  
Round Window Membrane ◽  
Therapeutic Drug ◽  
Constant Concentration ◽  
Sustained Drug Release ◽  
Drug Concentrations ◽  
Site Of Action ◽  
Two Phases

AbstractSustained local drug release and high local drug concentrations can be achieved by specially designed DDSs, which can be created for different applications. This results in therapeutic drug amounts at the site of action, simultaneously providing a very low drug amount in total. Bodily compartments that contain liquids may be used to transport the drugs from DDS into the tissue, such as the cochlea with the perilymph in the case of cochlea implants. However, predominantly dry environments, such as the middle ear, are lacking such a medium but may deliver enough moisture for the use of swellable DDS through the surrounding mucus membranes. Therefore, DDS with new functionalities are needed to ensure a sustained drug release. In this study, the release of dexamethasone out of a photopolymer system is presented. The system is built from UV-polymerized PEGDA followed by the incorporation of dexamethasone via swelling. The drug release is tested in vitro with isotonic NaCl solution for specified time periods, showing two phases: a swelling phase and a release phase. After the swelling phase the concentration of dexamethasone in the release medium was not controlled by diffusion, although sink conditions were ensured. In contrast, this system can be used to release the drug until equilibrium with a final medium concentration that is far below the solubility of dexamethasone. Hence, such DDS may be useful for dexamethasone delivery into the cochlea through the round window membrane by ensuring a constant concentration in the perilymph.

Astaxanthin-loaded polymer-lipid hybrid nanoparticles (ATX-LPN) Assessment of potential otoprotective effects

2020 ◽  
Author(s):  
Jiayi Gu ◽  
Yuming Chen ◽  
Ling Tong ◽  
Xueling Wang ◽  
dehong Yu ◽  
...  
Keyword(s):  
Inner Ear ◽  
Guinea Pigs ◽  
Round Window ◽  
Antioxidant Properties ◽  
Annexin V ◽  
Hybrid Nanoparticles ◽  
Protective Mechanism ◽  
Platinum Based Chemotherapy

Abstract Background Ototoxicity is one of the major side effects of platinum-based chemotherapy, especially cisplatin therapy. To date, no FDA approved agents to alleviate or prevent this ototoxicity are available. However, ototoxicity is generally believed to be produced by excessive generation of reactive oxygen species (ROS) in the inner ear, thus leading to the development of various antioxidants, which act as otoprotective agents. Astaxanthin (ATX) is an interesting candidate in the development of new therapies for preventing and treating oxidative stress-related pathologies, owing to its unique antioxidant capacity. Methods and Results In this study, we aimed to evaluate the potential antioxidant properties of ATX in the inner ear by using the HEI-OC1 cell line, zebrafish, and guinea pigs. Because ATX has poor solubility and cannot pass through round window membranes (RWM), we established lipid-polymer hybrid nanoparticles (LPN) for loading ATX. The LPN enabled ATX to penetrate RWM and maintain concentrations in the perilymph in the inner ear for 24 h after a single injection. ATX-LPN were found to have favorable biocompatibility and to strongly affect cisplatin-induced generation of ROS, on the basis of DCFHDA staining in HEI-OC1 cells. JC-1 and MitoTracker Green staining suggested that ATX-LPN successfully reversed the decrease in mitochondrial membrane potential induced by cisplatin in vitro and rescued cells from early stages of apoptosis, as demonstrated by FACS stained with Annexin V-FITC/PI. Moreover, ATX-LPN successfully attenuated OHC losses in cultured organ of Corti and animal models (zebrafish and guinea pigs) in vivo. In investigating the protective mechanism of ATX-LPN, we found that ATX-LPN decreased the expression of pro-apoptotic proteins (caspase 3/9 and cytochrome-c) and increased expression of the anti-apoptotic protein Bcl-2. In addition, the activation of JNK induced by CDDP was up-regulated and then decreased after the administration of ATX-LPN, while P38 stayed unchanged. Conclusions To best of our knowledge, this is first study concluded that ATX-LPN as a new therapeutic agent for the prevention of cisplatin-induced ototoxicity.

Defibrotide Inhibits Platelet Activation by Cathepsin G Released From Stimulated Polymorphonuclear Leukocytes

1992 ◽  
Vol 67 (06) ◽  
pp. 660-664 ◽  
Author(s):  
Virgilio Evangelista ◽  
Paola Piccardoni ◽  
Giovanni de Gaetano ◽  
Chiara Cerletti
Keyword(s):  
Platelet Activation ◽  
Polymorphonuclear Leukocytes ◽  
Direct Interaction ◽  
Cathepsin G ◽  
In Vivo Test ◽  
Cell Functions ◽  
Test Models ◽  
Antithrombotic Effects

SummaryDefibrotide is a polydeoxyribonucleotide with antithrombotic effects in experimental animal models. Most of the actions of this drug have been observed in in vivo test models but no effects have been reported in in vitro systems. In this paper we demonstrate that defibrotide interferes with polymorphonuclear leukocyte-induced human platelet activation in vitro. This effect was not related to any direct interaction with polymorphonuclear leukocytes or platelets, but was due to the inhibition of cathepsin G, the main biochemical mediator of this cell-cell cooperation. Since cathepsin G not only induces platelet activation but also affects some endothelial cell functions, the anticathepsin G activity of defibrotide could help to explain the antithrombotic effect of this drug.

scholarly journals The Effects of Round Window Membrane Injury and the Use of a Model Electrode Application on Hearing in Rats

2021 ◽  
pp. 014556132199018
Author(s):  
Murat Koc ◽  
Abdullah Dalgic ◽  
Mehmet Ziya Ozuer
Keyword(s):  
Hearing Loss ◽  
Cochlear Implant ◽  
Round Window ◽  
Mechanical Trauma ◽  
Round Window Membrane ◽  
Albino Rats ◽  
Topical Steroids ◽  
Distortion Product ◽  
Significant Difference ◽  
Group 3

Objective: To investigate the effects of the mechanical trauma to the round window, a model electrode inserted into the scala tympani on the cochlear reserve, and the efficacy of topical steroids in preventing hearing loss. Materials and Methods: 21 male Wistar Albino rats were equally categorized into three groups. In all groups an initial mechanical injury to round window was created. Only subsequent dexamethasone injection was administrated into the cochlea in the subjects of group 2 while a multichannel cochlear implant guide inserted into the cochlea prior to dexamethasone administration for group 3. Distortion product otoacoustic emissions (DPOAEs) were obtained prior to and immediately after the surgical injury, eventually on postoperative seventh day (d 7). Mean signal/noise ratios (S/Ns) obtained at 2000, 3000, and 4000 Hz were calculated. Data sets were compared with non-parametric statistical tests. Results: The early intraoperative mean S/Ns were significantly less than preoperative measurements for group 1 and 2; however, preoperative and postoperative d 7 average S/Ns did not differ. There was statistically significant difference between preoperative, intraoperative and postoperative d 7 average S/Ns for group 3. Conclusion: We observed that hearing was restored approximately to the preoperative levels following early postoperative repair. However, an electrode insertion into the cochlea via round window subsequent to mechanical trauma seems to cause a progressive hearing loss. Therefore, a special care must be taken to avoid the injury to the round window membrane in the course of the placement of a cochlear implant electrode and surgery for the chronic otitis media.

scholarly journals Cochlear Implantation Following Explorative Tympanotomy in Patients With Sudden Sensorineural Hearing Loss: Surgical Features and Audiological Outcomes

2021 ◽  
pp. 014556132110091
Author(s):  
Robin Rupp ◽  
Joachim Hornung ◽  
Matthias Balk ◽  
Matti Sievert ◽  
Sarina Müller ◽  
...  
Keyword(s):  
Hearing Loss ◽  
Connective Tissue ◽  
Sensorineural Hearing Loss ◽  
Cochlear Implantation ◽  
Round Window ◽  
Sudden Sensorineural Hearing Loss ◽  
Sensorineural Hearing ◽  
Round Window Membrane ◽  
Hearing Results ◽  
Round Window Niche

Objective: To investigate the anatomical status of the round window niche and hearing outcome of cochlear implantation (CI) after explorative tympanotomy (ExT) with sealing of the round window membrane in patients with sudden sensorineural hearing loss at a tertiary referral medical center. Methods: Between January 1, 2007, and July 30, 2020, 1602 patients underwent CI at our department. Out of these, all patients previously treated by ExT with sealing of the round window membrane because of unilateral sudden hearing loss were included in the study. A retrospective chart review was conducted concerning method of round window membrane sealing, intraoperative findings during CI, postoperative imaging, and hearing results. Results: Twenty one patients (9 females; 8 right ears; 54.3 years [± 12.9 years]) underwent ExT with sealing of the round window membrane with subsequent CI after 26.6 months (± 32.9 mo) on average. During CI, in 76% of cases (n = 16), the round window niche was blocked by connective tissue due to the previous intervention but could be removed completely in all cases. The connective tissue itself and its removal had no detrimental effects on the round window membrane. Postoperative computed tomography scan showed no electrode dislocation. Mean postoperative word recognition score after 3 months was 57.4% (± 17.2%) and improved significantly to 73.1% (± 16.4%, P = .005) after 2 years. Conclusion: Performing CI after preceding ExT, connective tissue has to be expected blocking the round window niche. Remaining tissue can be removed safely and does not alter the round window membrane allowing for a proper electrode insertion. Short- and long-term hearing results are satisfactory. Consequently, ExT with sealing of the round window membrane in patients with sudden sensorineural hearing loss does not impede subsequent CI that can still be performed safely.

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