Sustained Effect of Hyaluronic Acid in Subcutaneous Administration to the Cochlear Spiral Ganglion.
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.
Department of Otolaryngology Head and Neck Surgery, Keio University, Shinjuku-ku, Tokyo, Japan.
Yozo
Y
Inagaki
Department of Otolaryngology Head and Neck Surgery, Keio University, Shinjuku-ku, Tokyo, Japan.
Masato
M
Fujioka
Department of Otolaryngology Head and Neck Surgery, Keio University, Shinjuku-ku, Tokyo, Japan.
Sho
S
Kanzaki
Department of Otolaryngology Head and Neck Surgery, Keio University, Shinjuku-ku, Tokyo, Japan.
Kotaro
K
Watanabe
Department of Otolaryngology Head and Neck Surgery, Keio University, Shinjuku-ku, Tokyo, Japan.
Naoki
N
Oishi
Department of Orthopedics, School of Medicine, Keio University, Shinjuku-ku, Tokyo, Japan.
Go
G
Itakura
Department of Orthopedics, School of Medicine, Keio University, Shinjuku-ku, Tokyo, Japan.
Akimasa
A
Yasuda
Department of Physiology, School of Medicine, Keio University, Shinjuku-ku, Tokyo, Japan.
Shinsuke
S
Shibata
Department of Orthopedics, School of Medicine, Keio University, Shinjuku-ku, Tokyo, Japan.
Masaya
M
Nakamura
Department of Physiology, School of Medicine, Keio University, Shinjuku-ku, Tokyo, Japan.
Hirotaka James
HJ
Okano
Department of Physiology, School of Medicine, Keio University, Shinjuku-ku, Tokyo, Japan.
Hideyuki
H
Okano
Department of Otolaryngology Head and Neck Surgery, Keio University, Shinjuku-ku, Tokyo, Japan.
Kaoru
K
Ogawa
D000818:Animals; D003051:Cochlea / Q000187:drug effects* / Q000378:metabolism; D016503:Drug Delivery Systems / Q000379:methods; D007758:Ear, Inner / Q000187:drug effects / Q000378:metabolism; D006207:Half-Life; D006820:Hyaluronic Acid / Q000008:administration & dosage*; D007274:Injections, Intraperitoneal / Q000379:methods; D008156:Luciferases / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D013136:Spiral Ganglion / Q000187:drug effects* / Q000378:metabolism
D006820:Hyaluronic Acid; D008156:Luciferases