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

Jung-Ah Cho,Yu-Jung Hwang,Myung-Whan Suh,Bong-Jik Kim,Tae-Soo Noh,Shin-Wook Woo

doi:10.3390/ijms22115720

Abstract

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.

Highlights

Introduction iationsSensorineural hearing loss (SNHL) is associated with inner ear hair cell damage and can be caused by genetic disorders, infection, loud noises, or ototoxic drugs
The drug/vehicle completely filled the middle ear on the day of IT injection (post injection day (PID)0) in both groups
4 days later, no attenuation was found in group 1 (D and insulin-like growth factor 1 (IGF1) in saline), whereas some drug/vehicle was still visible in group 2 (microcapsulated D and IGF1 loaded in a cross-linked hyaluronic acid (HA) vehicle)

Summary

Introduction

Sensorineural hearing loss (SNHL) is associated with inner ear hair cell damage and can be caused by genetic disorders, infection, loud noises, or ototoxic drugs. There is no effective treatment for chronic SNHL except cochlear implants in selected cases. For acute onset hearing loss including sudden SNHL (SSNHL), steroid treatment can be effective. Systemic steroid therapy is the most common treatment for SSNHL [1,2] and a higher concentration of steroid is associated with a better treatment outcome [3,4]. Large doses of systemic steroid can lead to undesirable adverse effects [5]. Due to the blood-labyrinth barrier, it is difficult to maintain a sufficient level of steroid in the local target organ (cochlea) [6].

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