Pharmacokinetics and tissue distribution of neurotrophin 3 after intracochlear delivery
Rachael T Richardson, Qi-Ying Hu, Fuxin Shi, Nguyen Trung, James B Fallon, Brianna O Flynn, Andrew K Wise
JOURNAL OF CONTROLLED RELEASE | ELSEVIER SCIENCE BV | Published : 2019
Neurotrophin 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-..View full abstract
Awarded by Victorian Government, Australia
This 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. The authors would like to thank Scott Chambers, Ella Trang and Caitlin Singleton from the Bionics Institute, Melbourne, Australia, for technical assistance, Patricia WM Ho and Yao Sun from St Vincent's Institute, Melbourne, Australia for the use of the gamma counter and David Casley from ProSearch International, Melbourne, Australia, for technical assistance with protein radiolabelling and standards preparations.