Permeability of the Round Window Membrane Is Influenced by the Composition of Applied Drug Solutions and by Common Surgical Procedures

Mikulec, Anthony A.; Hartsock, Jared J.; Salt, Alec N.

doi:10.1097/mao.0b013e31818658ea

Cited by 68 publications

(70 citation statements)

References 29 publications

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“…For example, it is quite possible that RW membrane permeability increases with time of exposure to the nonphysiologic gel-fluid composition [Mikulec et al, 2008]. Similarly, the processes involved in drug elimination from the scalae may include drug movements to compartments, such as the modiolus, that decline with time as the compartment concentration increases.…”

Section: Resultsmentioning

confidence: 99%

Distribution of Dexamethasone and Preservation of Inner Ear Function following Intratympanic Delivery of a Gel-Based Formulation

Salt

Hartsock²,

Plontke³

et al. 2010

Audiol Neurotol

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111

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Intratympanic (IT) delivery of drugs to the ear is increasingly used for both clinical and research purposes. One limitation of IT delivery is that drugs are rapidly lost from the middle ear by a number of processes, so that prolonged delivery of drug is technically difficult. In the present study, the delivery characteristics of a poloxamer hydrogel formulation containing dexamethasone (dex) were evaluated. The gel is liquid at room temperature, allowing IT injection, but transitions to a gel at body temperature, providing a prolonged residence time in the middle ear. A 50-µl volume of control or dex-containing gel (dex-gel) was injected through the tympanic membrane of guinea pigs. Cochlear function was assessed with cochlear action potential and acoustic emission thresholds measured immediately, 6 or 24 h after IT gel injection. After 6- or 24-hour treatment with dex-gel, perilymph drug gradients along the cochlea were assessed by taking samples sequentially from the apex, and endolymph was sampled from the basal turn. Control gel injections caused small changes in sound field calibrations and functional measures for low-frequency stimuli, consistent with an induced conductive loss. Within 24 h, responses returned to normal. Twenty-four hours after dex-gel injection, low-frequency changes remained as the dex-gel was retained better in the middle ear, but there was no indication of high-frequency loss. While perilymph sample data showed that dex gradients were substantially lower than after single injections of dex solution, quantitative analysis of this result suggests that some dex may have entered the perilymph through the thin bone in the apical region of the cochlea. Endolymph levels of dex remained lower than those in the perilymph. This study confirms that a poloxamer hydrogel-based dex formulation provides an effective method for a prolonged delivery, providing a more uniform distribution of drug in the inner ear.

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Section: Resultsmentioning

confidence: 99%

Distribution of Dexamethasone and Preservation of Inner Ear Function following Intratympanic Delivery of a Gel-Based Formulation

Salt

Hartsock²,

Plontke³

et al. 2010

Audiol Neurotol

Self Cite

111

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“…However DMSO has been shown to be cytotoxic in cochlear organotypic cultures at concentrations between 0.5% and 6% [43] and may lead to reduced permeability [44].…”

Section: Discussionmentioning

confidence: 99%

Intratympanic Injections: An Unsolved Mystery

Parelkar¹,

Thorawade²,

Jagade³

et al. 2015

IJOHNS

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Aims: The aim of this study was to test the effectiveness of intratympanic dexamethasone injections as a treatment for severe disabling tinnitus and also observe its effect on hearing loss if any. Materials and Methods: Thirty patients with severe disabling tinnitus in the age group 20 to 60 years were selected and randomly assigned to receive intratympanic injections of a dexamethasone solution 4 mg/ml (0.5 ml) or isotonic saline (0.5 ml) solution under topical anaesthesia, once per week for 4 weeks using a zero degree endoscope. Improvement in tinnitus was assessed using a visual analog scale, considering 2-point improvement as significant and alteration in hearing if any was noted by pure tone audiometery before and after the therapy. Results: The improvement in tinnitus was not significant, with no alteration in audiometery reports. Conclusions: Intratympanic therapy is an attractive mode of treatment because of its highly targeted delivery, low concentration of the drugs required and a very good patient tolerance. Although there has been no breakthrough in intratympanic therapy for tinnitus or other otological conditions, accessibility to the inner ear through the semipermeable round window membrane holds many promises in the near future.

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“…Lipophilic steroids are more likely to 198 diffuse passively through the round windowcompared to hydrophilic steroids (Wang et al, 199 2011). Besides drug characteristics, other factors, including the thickness and the integrity of 200 the round window, osmolality of the formulation and the presence of preservatives (benzyl 201 alcohol) can affect round window permeability (Mikulec et al, 2008). These authors 202 estimated that benzyl alcohol enhanced round window permeability by a factor of 3 to 5 and 203 elevating osmolality from 300 to 620 mOsm/kg increased its permeability by a factor of 2 to 204 3.Moreover, Shih et al, (2013) successfully tested ultrasound-aided microbubbles to 205 temporarily increase round window permeability to fluorescently labelled biotin and 206 gentamicin.…”

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confidence: 99%