Pharmacokinetics and tissue distribution of neurotrophin 3 after intracochlear delivery

Simple item page
dc.contributor.authorRichardson, Rachael
dc.contributor.authorHu, Qi-Ying
dc.contributor.authorShi, Fuxin
dc.contributor.authorNguyen, Trung
dc.contributor.authorFallon, James
dc.contributor.authorFlynn, Brianna
dc.contributor.authorWise, Andrew
dc.date.accessioned2020-02-03T02:35:54Z
dc.date.available2020-02-03T02:35:54Z
dc.date.issued2019-02
dc.description.abstractNeurotrophin therapy has potential to reverse some forms of hearing loss. However, cochlear pharmacokinetic studies are challenging due to small fluid volumes. Here a radioactive tracer was used to determine neurotrophin- 3 retention, distribution and clearance after intracochlear administration. 125I- neurotrophin-3 was injected into guinea pig cochleae using a sealed injection technique comparing dosing volumes, rates and concentrations up to 750 μg/mL. Retention was measured by whole-cochlear gamma counts at five time points while distribution and clearance were assessed by autoradiography. Smaller injection volumes and higher concentrations correlated with higher retention of neurotrophin-3. Distribution of neurotrophin-3 was widespread throughout the cochlear tissue, decreasing in concentration from base to apex. Tissue distribution was nonuniform, with greatest density in cells lining the scala tympani and lower density in neural target tissue. The time constant for clearance of neurotrophin-3 from cochlear tissues was 38 h but neurotrophin-3 remained detectable for at least 2 weeks. Neurotrophin-3 was evident in the semi-circular canals with minor spread to the contralateral cochlea. This study is the first comprehensive evaluation of the disposition profile for a protein therapy in the cochlea. The findings and methods in this study will provide valuable guidance for the development of protein therapies for hearing loss.en_US
dc.description.sponsorshipThis research was funded by Decibel Therapeutics, Boston, USA and the National Health and Medical Research Council; Victorian Government, Australia, Project Grant GNT1142910. The Bionics Institute acknowledges the support it receives from the Victorian Government, Australia, through its Operational Infrastructure Support Program.en_US
dc.identifier.citationRichardson, R. T., Q. Y. Hu, F. Shi, T. Nguyen, J. B. Fallon, B. O. Flynn, and A. K. Wise. 2019. Pharmacokinetics and tissue distribution of neurotrophin 3 after intracochlear delivery. Journal of controlled release : official journal of the Controlled Release Society. 299: 53-63.en_US
dc.identifier.issn0168-3659
dc.identifier.urihttp://repository.bionicsinstitute.org:8080/handle/123456789/381
dc.language.isoenen_US
dc.publisherElsevier B.V.en_US
dc.subjectNeurotrophin-3en_US
dc.subjectCochleaen_US
dc.subjectDrug deliveryen_US
dc.subjectRadiolabelen_US
dc.subjectClearanceen_US
dc.subjectDistributionen_US
dc.subjectPharmacokineticsen_US
dc.subjectHearing lossen_US
dc.titlePharmacokinetics and tissue distribution of neurotrophin 3 after intracochlear deliveryen_US
dc.typeArticleen_US
Files
Original bundle
Now showing 1 - 1 of 1
Thumbnail Image
Name:
2019_Richardson_Pharmacokinetics.pdf
Size:
1.62 MB
Format:
Adobe Portable Document Format
Description:
Download
License bundle
Now showing 1 - 1 of 1
Thumbnail Image
Name:
license.txt
Size:
1.71 KB
Format:
Item-specific license agreed upon to submission
Description:
Download
Collections
BI publications