Local Long-Term Inner Ear Drug Delivery in Normal Hearing Guinea Pig—An Animal Model to Develop Preventive Treatment for Noise-Induced Hearing Loss

Abstract

Noise-induced hearing loss (NIHL) is one of the leading causes of sensorineural hearing loss with global importance. The current treatment of choice for patients with hearing problems is a hearing aid or a cochlear implant. However, there is currently no treatment to restore physiological hearing. The development of preventive drugs is currently the focus of hearing research. In order to test the efficacy of a drug, the active ingredient has to be applied at reliable concentrations over a period of time. Osmotic minipumps can provide local drug delivery into the perilymph. Combined with a cochlear implant or a tube, the implantation of the pumps may lead to increased hearing thresholds. Such surgery-related threshold shifts complicate the examination of other factors, such as noise. The aim of the present study was to develop an animal model for the examination of substances that potentially prevent NIHL. For this purpose, six male guinea pigs were unilaterally implanted with a silicon catheter with a hook-shaped microcannula at its tip, attached to an artificial perilymph containing osmotic minipump. One week after surgery, the animals were exposed to four hours of a musical piece, presented at 120 dB SPL, to induce a threshold shift. The implantation of the hook-delivery device caused a moderate threshold shift that allows to detect an additional noise-induced temporary threshold shift. This method enables to investigate drug effects delivered prior to the noise insult in order to establish a preventive strategy against noise-induced temporary threshold shifts. The established drug delivery approach allows the release of drugs into the inner ear in a known concentration and for a known duration. This provides a scientific tool for basic research on drug effects in normal hearing animals.

Dual Drug Delivery in Cochlear Implants: In Vivo Study of Dexamethasone Combined with Diclofenac or Immunophilin Inhibitor MM284 in Guinea Pigs

“…Anesthesia and medication after surgery were previously published in detail by Malfeld et al [ 28 ]. The implantation was performed under general anesthesia (intramuscular medetomidine hydrochloride 0.2 mg/kg, midazolam 1 mg/kg, and fentanyl 0.025 mg/kg) with previous sedation (oral diazepam 4 mg/kg).…”

Prevention of Noise-Induced Hearing Loss In Vivo: Continuous Application of Insulin-like Growth Factor 1 and Its Effect on Inner Ear Synapses, Auditory Function and Perilymph Proteins

“…The experimental setup was previously published in detail by Malfeld et al [43]. Therefore, published methods are only described briefly.…”

“…Osmotic minipumps (ALZET ® 2006, DURECT Corporation, Cupertino, CA, USA; pumping rate 0.15 µL/h) were filled and connected to a hook-delivery device (HDD) consisting of a commercially available silicone catheter (ALZET ® rat jugular catheter, DURECT Corporation, USA; 0.94 mm OD; 0.51 mm ID) and a small hook-shaped stainlesssteel tip (Nordson Optimum ® #7018433, Nordson Deutschland GmbH, Erkrath, Germany) with an outer diameter of 0.31 mm [43]. Pumps for control animals were filled with artificial perilymph (AP; 145 mM NaCl, 2.7 mM KCl, 2.0 mM MgSO 4 , 1.2 mM CaCl 2 , 5.0 mM HEPES, pH = 7.4 with 0.1% guinea pig serum albumin) [96].…”

“…The present study aimed to investigate the potential of continuous IGF-1 delivery to prevent noise-induced temporary threshold shift (TTS) and to improve the recovery thereafter. A moderate TTS-inducing noise trauma was applied [43]. As the biggest recovery of the synapses occurs during the first week after noise trauma [44] a recovery phase of seven days was used.…”

Emerging biotechnologies and biomedical engineering technologies for hearing reconstruction

“…Over the past few decades, various drug delivery systems and techniques have been developed and studied. Among them, nanoparticle-based delivery systems, [38][39][40][41] microsphere-based delivery systems, 42 and pump/catheter-based delivery systems [43][44][45] have been the most extensively presented.…”