Intratympanic injection of hydrogel nanodrug for the prevention and treatment of sensorineural hearing loss

Safe and efficient drug delivery to the inner ear has always been the focus of prevention and treatment of sensorineural deafness.The rapid development of nanodrug delivery systems based on hydrogel has provided a new opportunity.Among them,thermo-sensitive hydrogels promote the development of new dosage form for intratympanic injection.This smart biomaterial could transform to semisolid phase when the temperature increased.Thermo-sensitive hydrogel nanodrug delivery system is expected to achieve safe,efficient,and sustained inner ear drug administration.This article introduces the key techniques and the latest progress in this field.

Intratympanic dexamethasone injection for sudden sensorineural hearing loss in pregnancy

BACKGROUND As sudden sensorineural hearing loss(SSNHL)rarely occurs in pregnant women,there is a lack of knowledge and relevant research on its management.AIM To investigate the effect of intratympanic dexamethasone injection in the treatment of pregnant patients with SSNHL.METHODS A retrospective chart review was made for the period between June 2017 and August 2019 at our Department of Otorhinolaryngology-Head and Neck Surgery.Pregnant women who met the criteria for SSNHL were included and grouped based on the therapeutic modalities.The treatment group received intratympanic dexamethasone(2.5 mg)q.o.d.for a total of four times,while the control group received no medication other than bed rest and medical observations.All the patients were under close care of obstetricians.Pure-tone audiograms were performed before and after treatment.RESULTS Eleven patients who met the inclusion criteria were assigned to the treatment group(n=7)and the control group(n=4).The mean age of patients was 31.2±3.8 years;the right ear was affected in seven(63.64%)cases.Two patients(18.2%)suffered from vertigo,10(90.9%)suffered from tinnitus and 6(54.5%)suffered from aural fullness.The time from onset to clinic visit was relatively short,with a mean time of 1.3±0.9 d.All the women were within the second or third trimester;the average gestation period was 26.0±6.2 wk.The pure-tone averages at onset between the two groups were similar.After one wk of therapy,the treatment group had a curative rate of 57.1%and a significantly better hearing threshold and greater improvement compared to the control group(all P<0.05).Some patients experienced transient discomfort from intratympanic injections that disappeared after getting rest,while none had permanent complications.All patients delivered healthy full-term neonates with an average Apgar score of 9.7±0.5.CONCLUSION Intratympanic dexamethasone injections can be used as a first-line therapy in pregnant women with SSNHL.

Sudden sensorineural hearing loss treated with intratympanic dexamethasone injection

Objective To evaluate the effect of different protocols of intratympanic dexamethasone injection in patients with unilateral sudden sensorineural hearing loss (SSNHL) who have failed to respond to typical medical treatment (including systemic steroid treatment). Methods From January 2005 to January 2008, 71 patients who were diagnosed with unilateral SSNHL and failed typical medical treatment received intratympanic dexamethasone injection. Four injection protocols were employed: injection of 0.3 ml dexamethasone(5 mg / ml) three times a week for 3 weeks for a total dose of 13.5 mg (Group I, n=16); injection of 0.6 ml (5 mg / ml) dexamethasone three times a week for 3 weeks for a total dose of 27 mg (Group II, n=18); injection at 0.3 ml(5 mg/ml) week for 6 weeks for a total dose of 9 mg (Group III, n=18); injection at 0.3 ml (5 mg / ml) / 2 days for a total dose of 4.5 mg (Group IV n=19). Hearing recovery was assessed by pure tone audiogram. Results The total effective rate was 37.5%, 38.89%, 33.33% and 36.84% for each treatment protocol, respectively, with no statistical difference between them (P > 0.05). The results suggest that a total dose of 4.5 mg (injected once a week for 3 weeks) is the most adequate protocol, and increasing dose or injection frequency yields no additional benefits. Conclusion Intratympanic dexamethasone significantly improves the prognosis of SSNHL. Small dose at low injection frequency is sufficient. Further multicenter studies are needed to determine the standard treatment protocol.

Assessment of complications due to intratympanic injections

Objective: The purpose of the study is to report and to analyze the complications following intratympanic injections (ITI) of steroids. The occurrence rate of complications at different ITI sites, four quadrants of eardrum, was also compared. Methods: A retrospective clinical review in a medical center. Each patient received ITI twice in a week for 2e3 consecutive weeks as a salvage therapy for sudden sensorineural hearing loss. Post-injection complications, especially transient dizziness and vertigo, were recorded. Patients with acute or chronic vertigo episodes in 1 month were excluded. Results: A total of 59 patients with sudden sensorineural hearing loss and a total of 278 times of ITI were performed in 1 year. The post-injection complications included pain, tongue numbness, transient dizziness, vertigo, tinnitus, and a small persistent perforation. There was no significant difference in the occurrence of these complications between the injections sites on the 4 quadrants of the tympanic membrane. However, there was statistical significance in the post-injection vertiginous episode after IT injections to posterior-inferior quadrant (Q3) and posterior-superior quadrant (Q4) compared to anterior-superior quadrant (Q1) and anterior-inferior quadrant (Q2) (P Z 0.0113).

Therapeutic efficacy of methylprednisolone sodium succinate via diverse administration routes for mid-to high-frequency sudden sensorineural hearing loss

BACKGROUND Sudden sensorineural hearing loss(SSNHL),characterized by a rapid and unexplained loss of hearing,particularly at moderate to high frequencies,presents a significant clinical challenge.The therapeutic use of methylprednisolone sodium succinate(MPSS)via different administration routes,in combination with conventional medications,remains a topic of interest.AIM To compare the therapeutic efficacy of MPSS administered via different routes in combination with conventional drugs for the treatment of mid-to high-frequency SSNHL.METHODS The medical records of 109 patients with mid-to high-frequency SSNHL were analyzed.The patients were divided into three groups based on the route of administration:Group A[intratympanic(IT)injection of MPSS combined with mecobalamin and Ginkgo biloba leaf extract injection],Group B(intravenous injection of MPSS combined with mecobalamin and Ginkgo biloba leaf extract injection),and Group C(single IT injection of MPSS).The intervention effects were compared and analyzed.RESULTS The posttreatment auditory thresholds in Group A(21.23±3.34)were significantly lower than those in Groups B(28.52±3.36)and C(30.23±4.21;P<0.05).Group A also exhibited a significantly greater speech recognition rate(92.23±5.34)than Groups B and C.The disappearance time of tinnitus,time to hearing recovery,and disappearance time of vertigo in Group A were significantly shorter than those in Groups B and C(P<0.05).The total effective rate in Group A(97.56%)was significantly greater than that in Groups B and C(77.14%and 78.79%,χ^(2)=7.898,P=0.019).Moreover,the incidence of adverse reactions in Groups A and C was significantly lower than that in Group B(4.88%,3.03%vs 2.57%,χ^(2)=11.443,P=0.003),and the recurrence rate in Group A was significantly lower than that in Groups B and C(2.44%vs 20.00%vs 21.21%,χ^(2)=7.120,P=0.028).CONCLUSION IT injection of MPSS combined with conventional treatment demonstrates superior efficacy and safety compared to systemic administration via intravenous infusion and a single IT injection of MPSS.This approach effectively improves patients'hearing and reduces the risk of disease recurrence.

耳后注射神经节苷酯联合鼓室内注射甲泼尼龙治疗难治性突发性聋的临床研究

目的评价鼓室内注射甲泼尼龙联合耳后注射神经节苷酯治疗难治性突发性聋的临床疗效,为难治性突发性聋的治疗提供理论依据。方法以2019年9月~2022年1月于宜兴市人民医院和淮安市第二人民医院就诊的难治性突发性聋患者98例作为研究观察对象,随机分为观察组49例和对照组49例,观察组给予鼓室内注射甲泼尼龙联合耳后注射神经节苷脂治疗,对照组单纯行鼓室内注射甲泼尼龙治疗,通过随访调查,对两种不同治疗方法的临床效果进行对比分析。结果随访发现观察组患者治愈率明显高于对照组,差异具有显著性(P<0.05);两组患者不良反应发生率无明显差异,差异无统计学意义(P>0.05),对照组复发率明显高于观察组,差异显著(P<0.05)。结论鼓室内注射甲泼尼龙联合耳后注射神经节苷酯较单纯鼓室内注射甲泼尼龙治疗难治性突发性聋效果显著、复发率低,有一定的临床推广价值。

鼓室注射地塞米松磷酸钠注射液与注射用甲泼尼龙琥珀酸钠治疗突发性聋疗效观察及不良反应分析

目的探讨地塞米松磷酸钠注射液与注射用甲泼尼龙琥珀酸钠鼓室内注射治疗突发性聋的临床疗效并分析两种注射治疗后的不良反应。方法 2018年9月~2019年12月收治的单侧突发性聋患者94例,按数字表法随机分为A组(注射用甲泼尼龙琥珀酸钠组)和B组(地塞米松磷酸钠注射液组)各47例,分别行鼓室内注射注射用甲泼尼龙琥珀酸钠和鼓室内注射地塞米松磷酸钠注射液治疗,分析两组患者治疗前后纯音听阈值变化情况,并观察两组不良反应和空腹血糖变化情况。结果两组患者治疗后纯音听阈较治疗前均有明显改善(A组:t=9.86,P=0.001;B组:t=2.91,P=0.005),A组总有效率82.9%,B组总有效率为63.8%,两组总有效率比较,差异有统计学意义(χ2=4.41,P=0.036);两组总体不良反应率比较,差异无统计学意义(P>0.05);两组治疗前后空腹血糖变化比较,差异无统计学意义(P>0.05)。结论两种治疗方法均能改善突发性聋患者的纯音听阈,但注射用甲泼尼龙琥珀酸钠效果较地塞米松磷酸钠注射液更佳,两者的不良反应情况基本相仿。

两种激素鼓室灌注治疗重度以上突发性聋的疗效观察

近年来,越来越多的研究聚焦于鼓室内灌注激素治疗突发性聋（sudden deafness,SD）。2010年1月~2013年3月我科对99例重度以上SD患者分别给予全身或鼓室内注射激素治疗,现将治疗结果报道如下。

Audiological characteristics and exploratory treatment of a rare condition of acute-otitis-media-associated sudden sensorineural hearing loss

BACKGROUND Acute otitis media(AOM)is a common disease that is more prevalent in children.Most studies concerning AOM-associated sudden sensorineural hearing loss are case reports and retrospective in nature,hence the etiology of AOM-associated sudden hearing loss has not been fully established.AIM To analyze audiological characteristics of AOM-associated sudden hearing loss and evaluate efficacy of combined tympanostomy tube placement(TTP)and intratympanic methylprednisolone.METHODS Eight adult patients who were diagnosed with AOM-associated sudden hearing loss and ineffectively treated by conventional medical therapy were enrolled in this study.Basic data were collected,and pure tone audiometry was performed to assess the audiological characteristics.Combination therapy with TTP and intratympanic methylprednisolone injection was given to the patients.RESULTS Mixed or sensorineural hearing loss was observed at high frequencies(2–4 kHz).All the cases in this study were cured after TTP and intratympanic methylprednisolone.After treatment,the average hearing threshold at affected frequencies was significantly lower than those in the pretreatment group(P<0.05)and was similar to that in the healthy ears(P>0.05).CONCLUSION AOM rarely induces sudden sensorineural hearing loss.Combination therapy with TTP and intratympanic methylprednisolone injection may be effective after failure of conventional medical treatment.

Solid Lipid Nanoparticles Loaded with Edaravone for Inner Ear Protection After Noise Exposure

Background：Antioxidants and the duration of treatment after noise exposure on hearing recovery are important.We investigated the protective effects of an antioxidant substance,edaravone,and its slow-release dosage form,edaravone solid lipid nanoparticles （SLNs）,in steady noise-exposed guinea pigs.Methods：SLNs loaded with edaravone were produced by an ultrasound technique.Edaravone solution or edaravone SLNs were administered by intratympanic or intravenous injection after the 1st day of noise exposure.Guinea pigs were exposed to 110 dB sound pressure level （SPL） noise,centered at 0.25-4.0 kHz,for 4 days at 2 h/d.After noise exposure,the guinea pigs underwent auditory brainstem response （ABR） threshold measurements,reactive oxygen species （ROS） were detected in their cochleas with electron spin resonance （ESR）,and outer hair cells （OHCs） were counted with silvernitrate （AgNO3） staining at 1,4,and 6 days.Results：The ultrasound technique was able to prepare adequate edaravone SLNs with a mean particle size of 93.6 nm and entrapment efficiency of 76.7%.Acoustic stress-induced ROS formation and edaravone exerted a protective effect on the cochlea.Comparisons of hearing thresholds and ROS changes in different animal groups showed that the threshold shift and ROS generation were significantly lower in treated animals than in those without treatment,especially in the edaravone SLN intratympanic injection group.Conclusions：Edaravone SLNs show noticeable slow-release effects and have certain protective effects against noise-induced hearing loss （NIHL）.