A radiolab ele d drug tracing method to study neurotrophin-3 retention and distribution in the cochlea after nano-based local delivery

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dc.contributor.authorLam, Patrick
dc.contributor.authorGunewardene, Niliksha
dc.contributor.authorMa, Yutian
dc.contributor.authorCaruso, Frank
dc.contributor.authorNguyen, Trung
dc.contributor.authorFlynn, Brianna
dc.contributor.authorWise, Andrew
dc.contributor.authorRichardson, Rachael
dc.date.accessioned2021-02-08T03:40:06Z
dc.date.available2021-02-08T03:40:06Z
dc.date.issued2020-09
dc.description.abstractHearing loss is the most common sensory deficit worldwide with no approved therapeutics for treatment. Local neurotrophin delivery into the cochlea has shown great potential in protecting and repairing the sensory cells important for hearing. However, delivery of these factors into the inner ear at therapeutic levels over a sustained period of time has remained a challenge restricting clinical translation. We have developed a method to test the pharmacokinetics of neurotrophin released from porous silica particles called ‘supraparticles’ that can provide sustained release of neurotrophins to the inner ear. This report describes a radiolabeling method to examine neurotrophin retention and distribution in the cochlea. The neurotrophin was labeled with a radioactive tracer (iodine 125: 125I) and delivered into the cochlea via the supraparticle system. Gamma counts reveal drug levels and clearance in the intact cochlea, as well as accumulation in off-target organs (safety test). Autoradiography analyses using film and emulsion permit quantification and visualization of drug distribution at the cellular level. The method has a detection limit of 0.8 pg of radiolabeled neurotrophin-3 in cochlear sections exposed to film. The tracer 125I with a half-life of 59.4 days can be used to label other drugs/substances with a tyrosine residue and therefore be broadly applicable for long-term pharmacokinetic studies in other systems.en_US
dc.description.sponsorshipThis work was funded with support from the Department of Defense USA, Hearing Restoration Research Program, Translational Research Award W81XWH1810276, The Garnett Passe and Rodney Williams Memorial Foundation, the Australian National Health and Medical Research Council (NHMRC) (GNT 1142910), and the Australian Research Council Centre of Excellence in Convergent Bio-Nano Science and Technology (project number CE14010 0 036 ). F.C. acknowledges the award of an NHMRC Senior Principal Research Fellowship ( GNT1135806 ). The Bionics Institute acknowledges the support it receives from the Victorian Government, Australia, through its Operational Infrastructure Support Program.en_US
dc.identifier.citationLam, N. Gunewardene, Y. Ma, F. Caruso, T. Nguyen, B. Flynn, A. K. Wise, and R. Richardson. 2020. A radiolabeled drug tracing method to study neurotrophin-3 retention and distribution in the cochlea after nano-based local delivery. MethodsX: 101078.en_US
dc.identifier.issn2215-0161
dc.identifier.urihttp://repository.bionicsinstitute.org:8080/handle/123456789/411
dc.language.isoenen_US
dc.publisherElsevier B.V.en_US
dc.subjectDrug deliveryen_US
dc.subjectNanoparticlesen_US
dc.subjectNeurotrophinsen_US
dc.subjectHearing lossen_US
dc.subjectInner earen_US
dc.subjectCochleaen_US
dc.subjectProtein therapyen_US
dc.titleA radiolab ele d drug tracing method to study neurotrophin-3 retention and distribution in the cochlea after nano-based local deliveryen_US
dc.typeArticleen_US
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