Intratympanic Administration Research Articles

Dexamethasone nanocrystals-embedded hydroxypropyl methylcellulose hydrogel increases cochlear delivery and attenuates hearing loss following intratympanic injection

Herein, dexamethasone (DEX) nanocrystalline suspension (NS)-embedded hydrogel (NS-G) was constructed using a hydroxypropyl methylcellulose (HPMC) polymer to enhance cochlear delivery and attenuate hearing loss following intratympanic (IT) injection. Hydrophobic steroidal nanocrystals were prepared using a bead milling technique and incorporated into a polysaccharide hydrogel. The NS-G system with HPMC (average molecular weight, 86,000 g/mol; 15 mg/mL) was characterized as follows: rod-shaped drug crystalline; particle size <300 nm; and constant complex viscosity ≤1.17 Pa·s. Pulverization of the drug particles into submicron diameters enhanced drug dissolution, while the HPMC matrix increased the residence time in the middle ear cavity, exhibiting a controlled release profile. The IT NS-G system elicited markedly enhanced and prolonged drug delivery (> 9 h) to the cochlear tissue compared with that of DEX sodium phosphate (DEX-SP), a water-soluble prodrug. In mice with kanamycin- and furosemide-induced ototoxicity, NS-G markedly enhanced hearing preservation across all frequencies (8–32 kHz), as revealed by an auditory brainstem response test, compared with both saline and DEX-SP. Moreover, treatment with NS-G showed enhanced anti-inflammatory effects, as evidenced by decreased levels of inflammation-related cytokines. Therefore, the IT administration of DEX NS-loaded HPMC hydrogels is a promising strategy for treating hearing loss.

Comparing the Saccule-to-Utricle Ratio in Early- Versus Late-Stage Meniere's Disease Patients.

To compare the saccule-to-utricle ratio in early- versus late-stage Meniere's disease (MD) patients based on magnetic resonance imaging (MRI) images. In this retrospective study, we performed 3-dimensional real inversion recovery (3D-real IR) MRI 24 h after intratympanic gadolinium administration in unilateral MD patients at early-stage (n = 56) and late-stage (n = 70). Two radiologists independently graded endolymphatic hydrops (EH) and the saccule-to-utricle ratio inversion (SURI) was compared between the two groups. Furthermore, early-stage MD patients were further divided into two subgroups based on disease duration: ≤6 months (n = 20) and >6 months (n = 36) and the SURI was compared. Among the 56 patients in the early-stage group, 26 cases (46.43%) exhibited an enlarged saccule that is larger than the utricle, showing SURI. In contrast, among the late-stage MD, only four cases (5.71%) showed SURI (p < 0.001). In the early-stage MD subgroup with a disease duration of ≤6 months, the proportion of SURI was 70% (14/20), which was higher than that in the subgroup with a disease duration of >6 months (33.33%, 12/36, p = 0.02). SURI may serve as an effective imaging marker for diagnosis of early-stage MD. Our finding suggests that endolymphatic hydrops in MD may primarily originate from the saccule. Level 3 Laryngoscope, 2024.

Tactics of treatment the children with pharyngeal tonsil hypertrophy in combination with otitis media with effusion

Actual tactics of treatment for children with otitis media with effusion in combination with pharyngeal tonsil hypertrophy involve medical treatment and observation for 3 months. The next step is to resolve the issue of surgical treatment, however, there are differences in its scope: adenotomy, tympanopuncture/myringotomy, ventilation tubes introduce may be performed. The modern method of adenotomy (endoscopic power assisted adenotomy) has advantages over the classical one due to precision and better possibilities of removal of lymphoid tissue in the peritubar and perichoanal parts of the nasopharynx. The aim of our study was to increase the effectiveness of surgical treatment of children with otitis media with effusion and pharyngeal tonsil hypertrophy. Prospective results of treatment for 47 children with otitis media with effusion in combination with pharyngeal tonsil hypertrophy were studied. In 47 children with otitis media with effusion in combination with pharyngeal tonsil hypertrophy, endoscopic energy adenotomy with tympanopuncture with intratympanic administration of dexamethasone was performed. At the time of adenotomy, all children had been suffering from otitis media with effusion for 3 months or more, and medical treatment had no effect. The examination 1 month after the intervention established, the secretion in the tympanic cavity in 6.4% of children who subsequently require insertion of ventilation tube. In 80.8% of cases, normalization of intratympanic pressure was observed in one month after adenotomy with tympanopuncture. The average values of intratympanic pressure in patients in 2 and 4 weeks after the simultaneously intervention was (76.5±7.8) dPa and (51.3±8.5) dPa, respectively. Power assisted adenotomy with simultaneous tympanopuncture is an effective method of treating children with otitis media with effusion and pharyngeal tonsil hypertrophy and can be recommended for use in clinical practice. Keywords: otitis, otitis with effusion, tonsils hypertrophy, tonsil pharyngeal, adenotomy, inflammatory diseases of the upper respiratory ways.

Controlled release of dexamethasone from fibrin sealant for intratympanic administration in inner ear therapy

The aim of the present work was to show the sustainability of fibrin sealant in releasing dexamethasone and adjust the protocol for clinical application of the novel method in the treatment of Meniere's disease (MD) and sudden sensorineural hearing loss (SSHL). Gelation occurred shortly after mixing dexamethasone-containing fibrinogen with thrombin. Dexamethasone was constantly released for at least 16 d at a stable level after 7 d in protocol 1 (low-dose), while it was robustly released within 4 d and slowed afterward until 10 d in protocol 2 (high-dose). There were significant differences among the time points in Protocol 2 (p < 0.01, ANOVA), and the exponential model with the formula y = 15.299 * e−0.483 *t fits the association. The estimated concentration of dexamethasone released on 7 d in protocol 2 was slightly lower than that observed in protocol 1. The fibrin sealant is capable of constantly releasing dexamethasone with adjustable dynamics. Targeted and minimally invasive administration of the material can be achieved in the clinic by sequential injections of the fluids using a soft-tipped catheter.

Novel self-degradable prodrug blend thermogel for intratympanic drug delivery to treat inner ear diseases

The use of injectable hydrogel formulations for targeted drug delivery into the inner ear has gained considerable interest. In this study, we introduce a novel self-degradable prodrug blend thermogel system designed to deliver the anti-inflammatory drug, dexamethasone (DEX), in a controlled and safe manner for effective treatment of inner ear diseases. Our approach involves blending a thermogelling polymer, hexanoyl glycol chitosan (HGC), with a polymer prodrug, dexamethasone conjugated glycol chitosan (GC-DEX), to create injectable formulations suitable for intratympanic administration. Through extensive evaluation of the physicochemical and biological properties, we demonstrate that our thermogel formulations exhibit not only excellent thermogelling and injectable characteristics but also controlled release properties, resulting in enhanced drug absorption and prolonged drug concentration in the inner ear. The in vivo T2-weighted MRI Imaging further confirms the long-lasting stability of our thermogel formulations within the tympanic cavity, with a self-degradation period of approximately one month. Notably, guinea pigs treated with the HGC/GC-DEX formulation showed significant hearing recovery merely 7 days after noise exposure, accompanied by a reduction in outer hair cell loss. These promising results indicate the potential of our prodrug blend thermogel as an efficient delivery system for therapeutic agents in the inner ear.

Otologic safety of intratympanic N-acetylcysteine in an animal model.

N-acetylcysteine (NAC) is an anti-oxidant and mucolytic effective against bacterial biofilms, making it useful in the treatment of chronically discharging ears that are unresponsive to traditional treatment methods. The objective of this study was to evaluate the otologic safety of intratympanic NAC combined with Ciprodex® in an animal model. Baseline distortion product otoacoustic emissions (DPOAE) and auditory brainstem response (ABR) measurements were performed for both ears on thirteen guinea pigs from the animal care research facilities of the McGill University Health Center. This was followed by intratympanic administration of control solution (Ciprofloxacin 0.3%/Dexamethasone 0.1%) to the left ear and experimental solution (1.25% NAC/Ciprofloxacin 0.3%/Dexamethasone 0.1%) to the right ear. Three additional intratympanic injections were performed over the next fourteen days. DPOAE and ABR measurements were repeated 3-4 weeks after the initial procedure. Outcome measures included differences in DPOAE and ABR thresholds after intervention, clinical evidence of vestibular dysfunction and histological evidence of ototoxicity. There were no significant differences in the ABR thresholds and DPOAE results of the control and experimental ears at baseline and after intervention. There was neither clinical manifestation of vestibular dysfunction nor histological evidence of ototoxicity. Our study suggests that intratympanic 1.25% NAC with ciprofloxacin and dexamethasone is safe in guinea pigs and support its potential use in the treatment of chronically discharging ears. Further studies in humans are required to analyze its efficacy relative to conventional treatments. Animal Research.

Intratympanic Drug Application - Indication and Procedure

Neurootologic disorders of the inner ear associated with symptoms such as tinnitus, vertigo, and hearing loss are common and often cause significant distress to affected patients. Treatment options are usually limited. There are now some indications for which intratympanic drug application is a possible treatment option. Intratympanic drug administration is a simple, inexpensive therapy option with few side effects that can be used on an outpatient basis. Therefore, it should not be disregarded when indicated.

Sustained delivery of triamcinolone acetonide from a thermosensitive microemulsion gel system for the treatment of sensorineural hearing loss

Intratympanic administration for the delivery of steroids has been extensively studied but limited because of low permeability of the drug through the row window membrane. Here, to effectively deliver poorly soluble triamcinolone acetonide (TA), microemulsions (ME) were prepared from Capmul MCM (oil), Cremophor RH40 (surfactant), and tetraglycol (cosurfactant) based on solubility studies, emulsifying ability test, and pseudoternary phase diagrams. Microemulsion gel (MEG) was prepared by mixing TA-ME with a poloxamer hydrogel base. The physicochemical properties of ME and MEG formulations were characterized, and the toxicity and oto-protective effectiveness were evaluated in vitro and in vivo. The ME-3 formulation showed a small droplet size (16.5 ± 0.2 nm), narrow PDI (0.067 ± 0.041), and enhanced TA solubility (2619.7 ± 57.6 μg/g). The optimized MEG demonstrated temperature-dependent gelation with a gelation time of 208 ± 10 sec at 37 °C. Slow degradation of the gel matrix sustained release of TA from MEG compared to the ME formulation. Both TA-ME and TA-MEG were found to be nontoxic to NIH3T3 cells at the test concentrations (0 to 5 µg/mL), and biocompatible after intratympanic administration to mice. The incorporation of ME into thermosensitive hydrogels prolonged retention of TA at the site of administration until 6 days. As a consequence, the enhanced drug absorption into the cochlea in TA-MEG group (approximately 2 times higher than other groups) protected hair cells, spiral ganglion neurons, and stria vascular cells from cisplatin-induced damage. Therefore, this injectable TA-loaded MEG is an effective and safe vehicle for the sustained delivery of triamcinolone acetonide into the inner ear.

Live Imaging of the Dehydration Effect of Isosorbide on the Normal and Hydropic Guinea Pig Cochleae Using Optical Coherence Tomography.

To investigate the isosorbide-induced dehydration effect on the endolymphatic space by intratympanic administration of isosorbide. Isosorbide, an osmotic diuretic, is used orally as a typical conservative therapy for Menière's disease (MD) in Japan. The dehydration effect occurs 6 hours after isosorbide ingestion. Intratympanic administration of isosorbide resolves endolymphatic hydrops faster than oral ingestion. In addition, the dehydration effect has never been shown directly. Therefore, we investigated the dehydration effect of intratympanic administration of isosorbide on endolymphatic hydrops using optical coherence tomography. We used eight Hartley guinea pigs, divided into normal and hydrops groups. In the hydrops group, the animals underwent endolymphatic sac obliteration to create endolymphatic hydrops. We obtained midmodiolar section images of the cochleae using optical coherence tomography. Then, 50 to 70% isosorbide was sequentially administered intratympanically for 5 minutes, and the apical turn of the cochlea was observed. The relative midmodiolar cross-sectional area of the scala media was calculated for quantitative assessment of the endolymphatic space. In the normal group, 50% isosorbide had a slight but significant dehydration effect on the scala media; at 55 to 70%, Reissner's membrane became flat. In the hydrops group, 50% isosorbide slightly reduced endolymphatic hydrops; 65% flattened Reissner's membrane, and 70% slightly concaved it toward the basilar membrane. The results suggest that we could select the concentration of isosorbide according to the stage or severity of MD and relief from acute attack. Intratympanic administration of isosorbide may be a promising treatment for patients with MD.

Endolymphatic hydrops imaging and correlation with clinical characteristics, audiovestibular function and mental impairment in patients with Meniere’s disease

PurposeMR imaging was used to visualize the vestibular and cochlear endolymphatic hydrops in patients with Meniere’s disease (MD). The relationship between the degree of hydrops and clinical characteristics, audiovestibular function, anxiety and depression state in MD patients.Methods70 patients with definitely or probably unilateral Meniere’s disease received bilateral intratympanic gadolinium administration and MR scanning. The degree of bilateral vestibular and cochlea hydrops were analyzed and evaluated by three-dimensional real inversion recovery (3D-real IR) sequence, and the correlation between the grades of endolymphatic hydrops (EH) and disease course, vertigo grading assessment, the duration of vertigo, hearing loss level, caloric test, vestibular myogenic evoked potential (VEMP), electrocochleogram (EcoG), vertigo disability scale (physical, emotional, functional), anxiety and depression scale were studied.ResultsIt was found that the vestibule and cochlea EH of the affected and the contralateral ear had different degrees of hydrops and there was no statistical difference between the left and right vestibules. The degree of vestibule EH (V-EH) was significantly positively correlated with the degree of cochlear EH (C-EH). C-EH and hearing loss level were positively correlated with EcoG. There was positive correlation between vestibular EH and hearing loss level, VEMP, caloric test, disease course or vertigo duration. There was a negative relationship between Dizziness Handicap Inventory (Emotion) (DHI(E)) and VEMP. Self-rating Anxiety Scale (SAS) and Self-rating Depression Scale (SDS) scores were positive correlated with DHI(E) and DHI total scores in MD patients.ConclusionEndolymph-enhancing MRI was used as an important imaging method for the diagnosis of labyrinthine hydrops in Meniere’s disease. There were certain correlation between EH and the degree of vertigo attack, hearing loss level, vestibular function, and further changes in anxiety and depression emotion.

Meniere's disease in the practice of a neurologist

Meniere's disease (MD) is a chronic disease characterized by spontaneous recurrent attacks of vestibular vertigo, hearing loss, tinnitus, ear congestion, and other symptoms. Patients with acutely developed vestibular vertigo in most cases seek medical help from a neurologist. MD is characterized by the presence of endolymphatic hydrops, but there is no clear correlation between the severity of hydrops and the severity of clinical manifestations. The clinical presentation of MD is variable, with some patients having progressive auditory symptoms with occasional vertigo attacks, while others may have frequent vertigo attacks with minimal auditory symptoms. Diagnosis is based on a comprehensive assessment of the clinical picture, otoneurological examination, audiometry data, electrocochleography, vestibular evoked myogenic potentials; in complex cases, MRI of the inner ear with contrast enhancement is performed (currently, this method is not widely used in clinical practice) and MRI of the head to exclude intracranial pathology. Treatment of patients is aimed at relieving acute attacks of dizziness, informing the patient about the disease, prescribing a low-salt diet, betahistine or Arlevert administration to prevent attacks; in rare cases of ineffectiveness of conservative therapy, intratympanic administration of gentamicin or surgical methods of treatment are possible. The use of Arlevert in MD is discussed.

A review of bilateral sudden sensorineural hearing loss in pediatric patients.

Bilateral, sudden sensorineural hearing loss (SSNHL) in the pediatric population is a rare phenomenon potentially detrimental to language acquisition and social development. This study comprehensively reviews and analyzes existing literature to determine any correlation or commonality in etiologies, presentations, and management of this condition. PubMed, Cochrane, Scopus, and Web of Science databases were systematically searched for articles related to pediatric SSNHL from 1970 to 2021. Case series, case reports, and cohort studies were included. Data on patient demographics, etiology, diagnostic testing, management, and hearing recovery were collected. Excluding duplicates, 553 unique titles were identified by established search criteria, of which 342 titles were relevant to pediatric sudden hearing loss. Forty-six papers reported cases of bilateral SSNHL, totaling 145 individual cases. Not included in the analysis were 45 cases documented as non-organic hearing loss. The average age of the total 145 included patients was 8.5 years and 51 were male. Reported etiologies included cytomegalovirus (n=3), meningitis (n=13), mumps (n=5), ototoxin exposure (n=13), and enlarged vestibular aqueduct (n=9). Tinnitus (n=30) was the most reported concurrent symptom, followed by vertigo (n=21). Systemic steroid therapy was the most common treatment and, when follow up was reported, most patients (51.2%) had complete or partial recovery of hearing. This is a comprehensive review of pediatric bilateral SSNHL. Though often idiopathic, etiologies also include infectious, structural, and autoimmune. Treatment largely consists of systemic steroid therapy, with variables rates of recovery. Further studies on intratympanic administration of steroids may guide future treatment.

A Case of Eosinophilic Otitis Media Implanted with Bone-Anchored Hearing Aid

Eosinophilic otitis media (EOM) is characterized by the presence of highly viscous middle ear effusion containing eosinophils, and is usually associated with bronchial asthma. Intratympanic corticosteroid administration and/or systemic steroid administration are effective treatments. However, the middle ear effusion and progressive hearing loss are difficult to control, significantly affecting the patient’s quality of life. Therefore, appropriate care is important not only for controlling the middle ear effusion and otorrhea, but also for preventing the progression of hearing loss.A 46-year-old woman was referred to our hospital with suspected eosinophilic otitis media. She had a history of asthma and aspirin sensitivity. In addition, she had recurrent nasal polyps despite having undergone nasal polypectomy on two occasions. She was diagnosed as having bilateral EOM according to the diagnostic criteria. She was started on steroid treatment, but after showing initial response, the middle ear effusion recurred immediately after withdrawal of steroid treatment. Although the patient also had difficulty in communication because of bilateral hearing loss, she could not wear hearing aids because of the middle ear effusion. Hearing aids sometimes aggravate middle ear infection by blocking aeration, increasing the risk of sensorineural hearing loss. Therefore, we implanted a bone-anchored hearing aid (Baha®) in her right ear. Average hearing threshold of 500, 1000 and 2000 was 35 dB using Baha®. Although audiometry revealed deterioration of the bone-conduction threshold in the right ear at five years after the Baha® implantation, she still had sufficient bone conduction hearing using Baha® because of the preserved bone-conduction in the contralateral ear. The Baha® hearing system is a clinically effective and good hearing rehabilitative device for patients with EOM.

Ways of penetration of glucocorticosteroids from the tympanic cavity to the structures of the inner ear: A review

To date, in domestic and foreign literature, there are more and more reports of the successful use of glucocorticosteroids for the treatment of pathology of the inner ear by local intratympanic administration. Many methods are being developed to deliver drugs to the structures of the inner ear. As you know, the systemic administration of glucocorticosteroids has a number of contraindications and a large number of side effects, due to a wide spectrum of action. Exogenous glucocorticoids disrupt the natural balance of the hypothalamic-pituitary-adrenal system, interfering with the negative feedback regulation system, which requires a long time to fully restore. The intratympanic method of administering glucocorticosteroids makes it possible to bypass the above undesirable effects and at the same time provide the desired therapeutic effect on the vestibular and cochlear structures of the inner ear. With regard to the effect on the structures of the inner ear, intratympanic use of glucocorticosteroids turned out to be more effective than the systemic one, which is associated with the presence of a hematoperilymphatic barrier, comparable in its permeability to the blood-brain barrier. Moreover, when administered systemically, large doses of steroids are required to achieve a sufficient concentration of the drug in the fluids of the inner ear. To date, many questions remain regarding the routes by which the drug penetrates to the structures of the inner ear, the principles of distribution of the drug within the cochlear fluids, as well as the anatomical obstacles that may be encountered on the way to achieving the desired therapeutic effect. The purpose of this article is to highlight the current achievements in the field of research on the routes of penetration of drugs, in particular glucocorticosteroids, to the structures of the inner ear from the tympanic cavity.

Long-term exposure to high-concentration dexamethasone in the inner ear via intratympanic administration

The first-line treatment for inner ear disorders is usually oral/systemic steroids. Intratympanic steroid therapy is an alternative option; however, it requires multiple office visits owing to the short residence time of steroids in the inner ear (systemic: 24 h, intratympanic: 2–3 h). Therefore, intratympanic injections of higher steroid concentrations could result in longer drug exposure, providing better treatment outcomes. This study aimed to develop a prototype for high-concentration steroids and examine their safety and feasibility in vivo. Using wild-type Institute for Cancer Research mice, high-concentration steroids (50 mg/mL dexamethasone), typical steroid concentrations (3.3 mg/mL dexamethasone), and sterile saline were administrated into the middle ear cavity via tympanic membrane injection. Auditory brainstem response analysis, vestibular function tests, and morphological analyses were performed to examine the safety and utility of High-conc Dex. One month post-injection, the frequency-averaged auditory brainstem response thresholds of high-dose dexamethasone-treated mice were not significantly different from those of low-dose dexamethasone- and saline-treated mice at all tested frequencies. Furthermore, the total points on vestibular function tests were similar between the three groups. Morphologically, no damage to the inner ear/middle ear mucosa was observed in all groups. Two months post-injection, dexamethasone could still be detected in the high-dose dexamethasone group. Altogether, our data successfully demonstrates the feasibility and safety of high-dose dexamethasone for in vivo use in the middle ear and ensure that the drug localizes to the inner ear. Further research is warranted to develop this new treatment strategy and further characterize its effects in vivo.

Evaluation of prednisolone and prednisolone sodium succinate concentrations in human plasma and inner ear perilymph during cochlear implantation 24 h after intratympanic injection

Background The use of intratympanic (IT) steroids has drastically increased over the past 10–15 years to manage many otological pathologies. Objectives This study aimed to compare the concentrations of prednisolone and prednisolone sodium succinate (SS) in the plasma and inner ear perilymph of participants who underwent cochlear implantation 24 h after IT injection. Materials and methods It was a prospective comparative randomized study. Twenty participants received an IT injection of prednisolone SS ∼24 h before the cochlear implantation. The other five participants received an IT saline injection and represented the control group. Perilymph and blood were sampled during the cochlear implantation surgery. Results Both prednisolone and prednisolone SS were still present in perilymph ∼24 h after the IT administration. Only prednisolone was present in the blood plasma of seven participants (35%). Conclusion IT injection of prednisolone SS resulted in high perilymph concentrations of prednisolone and prednisolone SS, which could stay in the perilymph for at least 24 h. Using a mini-endoscope during the IT injection may effectively detect barriers infront of the round window membrane, increasing the drug concentration in the inner ear. Significance IT injection is an effective method for delivering prednisolone to the inner ear.

17O-labeled water distribution in the human inner ear: Insights into lymphatic dynamics and vestibular function.

We evaluated the inner ear distribution of 17O-labeled saline administered to the human tympanic cavity. Magnetic resonance imaging was performed after intratympanic administration in five healthy volunteers and one patient with cochlear endolymphatic hydrops. In all volunteers, 17O-labeled water permeated the cochlear basal turn and vestibule at 30 min and disappeared gradually within 2-4 h. All participants experienced positional vertigo lasting a few hours to a few days. Visualization of 17O-labeled water distribution in the endolymphatic space of the posterior ampulla showed indistinct separation of endolymph and perilymph in the cochlea and most of the vestibule in all participants. Intralabyrinthine distribution of 17O-labeled water differed from that in previous reports of intratympanically administered gadolinium-based contrast agent. 17O-labeled water in the endolymphatic space may cause heavier endolymph and positional vertigo. These results of this study may add new insights for investigating the distribution and the effects of molecules in the inner ear after the intratympanic administration in living humans.

Interpretation of consensus on MRI of endolymphatic hydrops in patients with suspected hydropic ear disease and domestic research progress

Endolymphatic hydrops（EH） is considered the histological hallmark of Meniere's disease. Visualization of EH has been achieved by special sequences of inner ear magnetic resonance imaging（MRI） with gadolinium-based contrast-agent via intravenous or intratympanic administration. Although it has been applied for more than ten years since 2007, a unified view on this technique has not yet been achieved. In 2022, Yang Jun and Duan Maoli et al led the organization to write the international expert consensus on MRI of EH. This article interprets the main contents and reports related progress.

Microfluidic Preparation of Gelatin Methacryloyl Microgels as Local Drug Delivery Vehicles for Hearing Loss Therapy.

Local drug delivery has become an effective method for disease therapy in fine organs including ears, eyes, and noses. However, the multiple anatomical and physiological barriers, unique clearance pathways, and sensitive perceptions characterizing these organs have led to suboptimal drug delivery efficiency. Here, we developed dexamethasone sodium phosphate-encapsulated gelatin methacryloyl (Dexsp@GelMA) microgel particles, with finely tunable size through well-designed microfluidics, as otic drug delivery vehicles for hearing loss therapy. The release kinetics, encapsulation efficiency, drug loading efficiency, and cytotoxicity of the GelMA microgels with different degrees of methacryloyl substitution were comprehensively studied to optimize the microgel formulation. Compared to bulk hydrogels, Dexsp@GelMA microgels of certain sizes hardly cause air-conducted hearing loss in vivo. Besides, strong adhesion of the microgels on the round window membrane was demonstrated. Moreover, the Dexsp@GelMA microgels, via intratympanic administration, could ameliorate acoustic noise-induced hearing loss and attenuate hair cell loss and synaptic ribbons damage more effectively than Dexsp alone. Our results strongly support the adhesive and intricate microfluidic-derived GelMA microgels as ideal intratympanic delivery vehicles for inner ear disease therapies, which provides new inspiration for microfluidics in drug delivery to the fine organs.

The impact of eustachian tube function on intra-tympanic steroid administration.

This study investigated the impact of eustachian tube (ET) function (ETF) on therapeutic success on candidates for intra-tympanic administration of steroids (ITAoS), due to idiopathic sudden sensorineural hearing loss (ISSNHL). Medical chart review in two university-affiliated medical centers was performed. Included were consecutive adult patients diagnosed with unilateral ISSNHL between 2012 and 2019 who were treated with ITAoS due to incomplete or no recovery following systemic steroidal therapy. ETF was assessed by means tympanometry, before the initiation of ITAoS. The cohort was divided into an ET dysfunction group (ETD(+)) and a functioning ET group (control: ETD(-)). The audiologic response to treatment was recorded at the last follow-up. A total of 64 suitable patients [median (interquartile, IQR) age 49 (38-63) years] were enrolled. The ETD(+) group included 20 patients and the remaining 44 patients served as controls. Demographic and clinical parameters were not significantly different between the two groups at presentation. Hearing thresholds were improved significantly better, at frequencies 250, 500, 1, 2, 4, and 8kHz (p = 0.001-0.040) in the ETD(+) group. ETD(+) is associated with better efficacy of ITAoS.