ヒアルロン酸を用いた徐放性薬剤による蝸牛らせん神経節へのDrug delivery systemの構築を目標とし, 徐放剤の使用や投与方法による内耳薬物動態の違いを確認して蝸牛へのヒアルロン酸の徐放効果について検討した。結果, マウス背部へのヒアルロン酸抱合ルシフェリン投与は, 当量の生理食塩水を溶媒としたルシフェリン溶液の同部位への皮下投与, 腹腔内投与と比べて蝸牛局所での最高濃度到達時間, 半減期がともに有意に延長しており, 徐放剤として極めて有用であることが示された。同時に, 同実験系が内耳へのdrug deliveryの評価に有用で, 簡便かつ実用的な実験系であることが示唆された。
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.
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