1. Enhanced Drug Delivery to the Inner Ear
Daniel Choo, MD

2. Enhanced Drug Delivery to the Inner Ear
Problem
Injecting a drug solution intra-tympanically (in order to treat the inner ear) is poorly controlled due to Eustachian tube clearance of the liquid. For most clinical conditions (e.g. sensorineural hearing loss), a more controlled and reliable method of delivering a long-acting medication in the inner ear is desired.

3. Enhanced Drug Delivery to the Inner Ear
Background
Congenital hearing loss represents the most common neurological birth defect in the US; with 2 per 1000 births demonstrating a severe or worse sensorineural hearing loss (SNHL)
Great strides have been made in determining the may possible causes of congenital hearing loss (genetic mutations, developmental anomalies of the inner ear, etc)
Attention has increasingly focused on Cytomelagovirus (CMV) infection as a major cause of congenital SNHL; and notably, a potentially treatable form of SNHL

4. Enhanced Drug Delivery to the Inner Ear
Background
Congenital cytomegalovirus (CMV) infection is a major public health concern. CMV causes a spectrum of serious sequelae including mental retardation, cerebral palsy, enlargement of the liver and spleen, retinitis, petechiae, microcephaly, brain calcifications and SNHL.
Some of these conditions can be mitigated (or possibly reversed in some instances) with proper antiviral therapy

5. Need statement
A none invasive device delivering a long-acting medication in the inner for home setting and outpatient use

6. ENT Journal 1996
Antiviral Ther 2014
Curr Drug Del 2015
PlosOne 2016

7. Constraints Avoid serious toxicities of systemic drug exposure
Enhanced Drug Delivery to the Inner Ear
Constraints
Avoid serious toxicities of systemic drug exposure
Deliver pharmacologically relevant drug levels to the inner ear – vehicle will be important
Avoid inducing a hearing loss (permanent or temporary)
Avoid causing inflammation of the middle ear space

8. Enhanced Drug Delivery to the Inner Ear
Summary
Medical treatment of the inner ear via intratympanic drug delivery presents a clinical opportunity to innovatively apply novel nanotechnologies in order to achieve safer and more controlled drug delivery to the inner ear while also avoiding systemic toxicities seen with oral and parenteral drug administration
Congenital CMV infection with SNHL can potentially be treated using intratympanic antiviral therapy using hydrogel-mediated drug delivery to the round window membrane

9. Enhanced Drug Delivery to the Inner Ear
Potential solutions
Develop a mechanism for enhanced drug delivery to the inner ear
Direct delivery of a drug to the target organ (i.e. the inner ear) would avoid the serious toxicities of some systemic drugs (e.g. bone marrow suppression, renal toxicity) while delivering pharmacologically relevant drug levels to the inner ear
Research is being completed on a temperature-sensitive, hydrogel that remains in the middle ear (rather than being cleared down the Eustachian tube) allowing a more controlled (and prolonged) release of the pharmaceutical to the inner ear
another option is to provide a nanoparticle encapsulated drug to slowly release the medicine