Enhanced Drug Delivery to the Inner Ear Daniel Choo, MD

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.

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

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

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

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

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

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

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