A radiolabeled drug tracing method to study neurotrophin-3 retention and distribution in the cochlea after nano-based local delivery
Patrick Lam,
Niliksha Gunewardene,
Yutian Ma,
Frank Caruso,
Trung Nguyen,
Brianna Flynn,
Andrew K. Wise,
Rachael T. Richardson
Affiliations
Patrick Lam
Bionics Institute, East Melbourne, Victoria 3002, Australia; Department of Medical Bionics, University of Melbourne, Fitzroy, Victoria 3065, Australia
Niliksha Gunewardene
Bionics Institute, East Melbourne, Victoria 3002, Australia; Department of Medical Bionics, University of Melbourne, Fitzroy, Victoria 3065, Australia
Yutian Ma
Bionics Institute, East Melbourne, Victoria 3002, Australia; ARC Centre of Excellence in Convergent Bio-Nano Science and Technology, and the Department of Chemical Engineering, University of Melbourne, Parkville, Victoria 3010, Australia
Frank Caruso
ARC Centre of Excellence in Convergent Bio-Nano Science and Technology, and the Department of Chemical Engineering, University of Melbourne, Parkville, Victoria 3010, Australia
Trung Nguyen
Bionics Institute, East Melbourne, Victoria 3002, Australia; Department of Medical Bionics, University of Melbourne, Fitzroy, Victoria 3065, Australia
Brianna Flynn
Bionics Institute, East Melbourne, Victoria 3002, Australia; Department of Medical Bionics, University of Melbourne, Fitzroy, Victoria 3065, Australia
Andrew K. Wise
Bionics Institute, East Melbourne, Victoria 3002, Australia; Department of Medical Bionics, University of Melbourne, Fitzroy, Victoria 3065, Australia; University of Melbourne, Department of Otolaryngology, The Royal Victorian Eye and Ear Hospital, East Melbourne, VIC 3002, Australia
Rachael T. Richardson
Bionics Institute, East Melbourne, Victoria 3002, Australia; Department of Medical Bionics, University of Melbourne, Fitzroy, Victoria 3065, Australia; University of Melbourne, Department of Otolaryngology, The Royal Victorian Eye and Ear Hospital, East Melbourne, VIC 3002, Australia; Corresponding author at: Bionics Institute, East Melbourne, Victoria 3002, Australia.
Hearing 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.
