Effect and Biocompatibility of a Cross-Linked Hyaluronic Acid and Polylactide-co-glycolide Microcapsule Vehicle in Intratympanic Drug Delivery for Treating Acute Acoustic Trauma

The treatment of acute hearing loss is clinically challenging due to the low efficacy of drug delivery into the inner ear. Local intratympanic administration of dexamethasone (D) and insulin-like growth factor 1 (IGF1) has been proposed for treatment, but they do not persist in the middle ear because they are typically delivered in fluid form. We developed a dual-vehicle drug delivery system consisting of cross-linked hyaluronic acid and polylactide-co-glycolide microcapsules. The effect and biocompatibility of the dual vehicle in delivering D and IGF1 were evaluated using an animal model of acute acoustic trauma. The dual vehicle persisted 10.9 times longer (8.7 days) in the middle ear compared with the control (standard-of-care vehicle, 0.8 days). The dual vehicle was able to sustain drug release over up to 1 to 2 months when indocyanine green was loaded as the drug. One-third of the animals experienced an inflammatory adverse reaction. However, it was transient with no sequelae, which was validated by micro CT findings, endoscopic examination, and histological assessment. Hearing restoration after acoustic trauma was satisfactory in both groups, which was further supported by comparable numbers of viable hair cells. Overall, the use of a dual vehicle for intratympanic D and IGF1 delivery may maximize the effect of drug delivery to the target organ because the residence time of the vehicle is prolonged.

The Use of Hyperbaric Oxygen Therapy and Corticosteroid Therapy in Acute Acoustic Trauma: 15 Years’ Experience at the Czech Military Health Service

Background: Acute acoustic trauma (AAT) ranks, among others, as one common cause of inner ear function impairment, especially in terms of military personnel, who are at an increased exposure to impulse noises from firearms. Aim of this study: 1. We wanted to demonstrate whether early treatment of AAT means a higher chance for the patient to improve hearing after trauma. 2. We find the answer to the question of whether hyperbaric oxygen therapy (HBO2) has a positive effect in the treatment of AAT. Methods: We retrospectively analyzed data for the period 2004–2019 in patients with AAT. We evaluated the therapeutic success of corticosteroids and HBO2 in a cohort of patients with AAT n = 108 patients/n = 141 affected ears. Results: Hearing improvement after treatment was recorded in a total of 111 ears (79%). In terms of the data analysis we were able to ascertain, utilizing success of treatment versus timing: within 24 h following the onset of therapy in 56 (40%) ears—54 (96%) ears had improved; within seven days following the onset the therapy was used in 55 (39%) ears—41 (74%) ears had improved; after seven days the therapy started in 30 (21%) ears—16 (53%) ears had improved. Parameter latency of the beginning of the treatment of AAT was statistically significant (p = 0.001 and 0.017, respectively). The success of the medical protocols was apparent in both groups—group I (treated without HBO2): n = 61 ears, of which 50 (82%) improved, group II (treated with HBO2): n = 73 ears, of which 56 (77%) improved. Group II shows improvement at most frequencies (500–2000 Hz). The most serious sensorineural hearing loss after AAT was at a frequency of 6000 Hz. Conclusion: Analysis of our data shows that there is a statistically significant higher rate of improvement if AAT treatment was initiated within the first seven days after acoustic trauma. Early treatment of AAT leads to better treatment success. HBO2 is considered a rescue therapy for the treatment of AAT. According to our recommendation, it is desirable to start corticosteroid therapy immediately after acoustic trauma. If hearing does not improve during the first seven days of corticosteroid therapy, then HBO2 treatment should be initiated.

Hsp70/Bmi1-FoxO1-SOD Signaling Pathway Contributes to the Protective Effect of Sound Conditioning against Acute Acoustic Trauma in a Rat Model

Sound conditioning (SC) is defined as “toughening” to lower levels of sound over time, which reduces a subsequent noise-induced threshold shift. Although the protective effect of SC in mammals is generally understood, the exact mechanisms involved have not yet been elucidated. To confirm the protective effect of SC against noise exposure (NE) and the stress-related signaling pathway of its rescue, we observed target molecule changes caused by SC of low frequency prior to NE as well as histology analysis in vivo and verified the suggested mechanisms in SGNs in vitro. Further, we investigated the potential role of Hsp70 and Bmi1 in SC by targeting SOD1 and SOD2 which are regulated by the FoxO1 signaling pathway based on mitochondrial function and reactive oxygen species (ROS) levels. Finally, we sought to identify the possible molecular mechanisms associated with the beneficial effects of SC against noise-induced trauma. Data from the rat model were evaluated by western blot, immunofluorescence, and RT-PCR. The results revealed that SC upregulated Hsp70, Bmi1, FoxO1, SOD1, and SOD2 expression in spiral ganglion neurons (SGNs). Moreover, the auditory brainstem responses (ABRs) and electron microscopy revealed that SC could protect against acute acoustic trauma (AAT) based on a significant reduction of hearing impairment and visible reduction in outer hair cell loss as well as ultrastructural changes in OHCs and SGNs. Collectively, these results suggested that the contribution of Bmi1 toward decreased sensitivity to noise-induced trauma following SC was triggered by Hsp70 induction and associated with enhancement of the antioxidant system and decreased mitochondrial superoxide accumulation. This contribution of Bmi1 was achieved by direct targeting of SOD1 and SOD2, which was regulated by FoxO1. Therefore, the Hsp70/Bmi1-FoxO1-SOD signaling pathway might contribute to the protective effect of SC against AAT in a rat model.

Biocompatibility and Therapeutic Effect of 3 Intra-Tympanic Drug Delivery Vehicles in Acute Acoustic Trauma

<b><i>Introduction:</i></b> The aim of this study was to assess the biocompatibility of several intra-tympanic (IT) drug delivery vehicles and to compare hearing outcomes. <b><i>Materials and Methods:</i></b> After acute acoustic trauma, rats were treated with IT 10 mg/mL dexamethasone phosphate (D) and divided into the following groups for drug delivery: saline + D (<i>n</i> = 15), hyaluronic acid (HA) + D (<i>n</i> = 17), and methoxy polyethylene glycol-<i>b</i>-polycaprolactone block copolymer (MP) + D (<i>n</i> = 24). <b><i>Results:</i></b> No inflammation was found in the saline + D or HA + D groups. The duration of vehicle/drug persistence in the bulla was significantly longer for the MP + D (47.5 days) and HA + D groups (1.8 days) than for the saline + D group (&#x3c;1 day). The tympanic membrane was significantly thicker in the MP + D group than in the saline + D and HA + D groups. The proportion of ears with good hearing outcome was significantly higher (63.6%) in the HA + D group than in the MP + D group. The number of hair cells in the hearing loss (HL) control group was significantly lower than in the MP + D group. <b><i>Discussion/Conclusion:</i></b> HA shows great potential as a biocompatible vehicle for D delivery via the IT route, without an inflammatory reaction and with better hearing outcomes. Considering inflammation and hearing, MP may not be a good candidate for IT drug delivery.

Application of Hyperbaric Therapy Following Acoustic Trauma – Case Report

Introduction: Acoustic trauma is noise-induced hearing damage. It can occur as a result of a strong sound stimulus or explosion, which causes a pressure wave, which causes in the organism the damage of structures filled with air, e.g. tympanic membrane. Acoustic trauma has many consequences in the form of: deterioration or complete loss of hearing, tinnitus, crackling, feeling of confusion and constant fatigue, headaches and dizziness. It also has a significant impact on the quality of life – it hinders people-to-people contacts and prevents professional activities and may be the cause of depressive disorders. Acoustic trauma can be treated, among others, through the use of hyperbaric therapy, which has a wide spectrum of activity in many fields of medicine. Aim: The aim of the study was to present the legitimacy of using oxygen treatment at increased pressure in a patient after acute acoustic trauma. Material and method: The study was conducted at Hyperbaric Therapy Center CREATOR in Lodz (Didactic and Research Center of the Medical University of Lodz). As a research method, case study was used in an individual patient after an acoustic trauma. Using the extended interview questionnaire and analysis of available medical records. Conclusion: Hyperbaric therapy may be a useful method in the treatment of acute acoustic trauma.