Abstract
Objectives: The spatiotemporal distribution of drugs in the inner ear has not fully been characterized because of the area’s small size and complicated compartments. In the present study, we investigate the pharmacokinetics of a small molecule conjugated with different amounts of carrier in the cochlea by using transgenic technology and the IVIS Imaging System. Methods: Luciferin, a 280 MW substrate of luciferase, was conjugated with different MW of hyaluronic acid and was subcutaneously administered to the transgenic mouse, GFAP-luc, which expresses luciferase specifically in the cochlear spiral ganglion cells. Bioluminescence produced by a chemical reaction of luciferin-luciferase was monitored using the Xenogen-IVIS 100. Results: The peak photon count decreased dose-dependently on the MW of hyaluronic acid, whereas the duration was prolonged. Conclusions: Our imaging system successfully detected differences in the pharmacokinetics of luciferin in the inner ear. The sustained-release effect of hyaluronic acid was observed and differed by its MW. The result suggests the clinical significance of hyaluronic acid for controlling drug delivery to the cochlea.
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