Sustained Effect of Hyaluronic Acid in Subcutaneous Administration to the Cochlear Spiral Ganglion.

Yozo Inagaki,Shinsuke Shibata,Masaya Nakamura,Hirotaka James Okano,Sho Kanzaki,Go Itakura,Kotaro Watanabe,Masato Fujioka,Naoki Oishi,Hideyuki Okano,Akimasa Yasuda,Kaoru Ogawa,Makoto Sato

doi:10.1371/journal.pone.0153957

Abstract

The spatiotemporal distribution of drugs in the inner ear cannot be precisely evaluated because of its small area and complex structure. In the present study, we used hyaluronic acid (HA)-dispersed luciferin to image transgenic mice and to determine the effect of HA on controlled drug delivery to the cochlea. GFAP-luc mice, which express luciferase in cochlear spiral ganglion cells, were subcutaneously administered HA-luciferin (HA-sc) or luciferin dissolved in saline (NS-sc) or intraperitoneally administered luciferin dissolved in saline (NS-ip). The bioluminescence of luciferin was monitored in vivo in real time. The peak time and half-life of fluorescence emission were significantly increased in HA-sc-treated mice compared with those in NS-sc- and NS-ip-treated mice; however, significant differences were not observed in peak photon counts. We detected differences in the pharmacokinetics of luciferin in the inner ear, including its sustained release, in the presence of HA. The results indicate the clinical potential of using HA for controlled drug delivery to the cochlea.

Highlights

The inner ear is a minute organ surrounded by bones and comprises a tight junction that serves as a blood—inner ear barrier between the inner ear fluid and systemic circulation
We found that GFAP-Luc transgenic mice expressed luciferase in peripheral glial cells of the auricular skin and the cochlear spiral ganglion in the head and neck areas
Our findings indicate that intraperitoneally introduced luciferin passed through these barriers in the same time required for subcutaneous administration

Summary

Introduction

The inner ear is a minute organ surrounded by bones and comprises a tight junction that serves as a blood—inner ear barrier between the inner ear fluid and systemic circulation. These characteristics impede efficient drug delivery, creating an urgent need to develop a topical drug delivery system (DDS) that enables efficient transport and subsequent maintenance of high drug concentrations to a part of the inner ear. Researchers face daunting obstacles presented by the anatomical, histological, and structural limitations of the inner ear that make it technically difficult to continuously monitor the concentrations of topically administered drugs without disrupting normal physiological pharmacokinetics.

Methods

Results

Conclusion