TY - JOUR
T1 - Sustained effect of hyaluronic acid in subcutaneous administration to the cochlear spiral ganglion
AU - Inagaki, Yozo
AU - Fujioka, Masato
AU - Kanzaki, Sho
AU - Watanabe, Kotaro
AU - Oishi, Naoki
AU - Itakura, Go
AU - Yasuda, Akimasa
AU - Shibata, Shinsuke
AU - Nakamura, Masaya
AU - James Okano, Hirotaka
AU - Okano, Hideyuki
AU - Ogawa, Kaoru
N1 - Funding Information:
We are grateful to Ayano Mitsui for technical assistance and Makoto Hosoya for helpful comments and discussions. This work was supported by a MEXT KAKENHI Grant-in-Aid for Young Scientists (B) (25861590) to Y.I, a MEXT KAKENHI Grant-in-Aid for Scientific Research (C) (24592560) and (B) (15H04991), grants from the MHLW (Comprehensive Research on Disability Health and Welfare) and the Takeda Science Foundation to M.F, and a grant from MEXT KAKENHI to S.K.
Publisher Copyright:
© 2016 Inagaki et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
PY - 2016/4
Y1 - 2016/4
N2 - 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-sctreated 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.
AB - 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-sctreated 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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U2 - 10.1371/journal.pone.0153957
DO - 10.1371/journal.pone.0153957
M3 - Article
C2 - 27099926
AN - SCOPUS:84964594763
SN - 1932-6203
VL - 11
JO - PloS one
JF - PloS one
IS - 4
M1 - e0153957
ER -