Drug Delivery for Treatment of Inner Ear Disease: Current State of Knowledge

Abstract

Delivery of medications to the inner ear has been an area of considerable growth in both the research and clinical realms over the past several decades. Systemic delivery of medication destined for treatment of the inner ear is the foundation upon which newer delivery techniques have been developed. Due to systemic side effects, investigators and clinicians have begun developing and utilizing techniques to deliver therapeutic agents locally. Alongside the now commonplace use of intratympanic gentamicin for Meniere's disease and the emerging use of intratympanic steroids for sudden sensorineural hearing loss, novel technologies, such as hydrogels and nanoparticles, are being explored. At the horizon of inner ear drug delivery techniques, intracochlear devices that leverage recent advances in microsystems technology are being developed to apply medications directly into the inner ear. Potential uses for such devices include neurotrophic factor and steroid delivery with cochlear implantation, RNA interference technologies, and stem cell therapy. The historical, current, and future delivery techniques and uses of drug delivery for treatment of inner ear disease serve as the basis for this review.

Development of a drug delivery system for the inner ear using poly(amino acid)-based nanoparticles

“…Current strategies in various stages of development and use include intratympanic injection, the Silverstein Microwick (Micromedics, St. Paul, MN), microcatheter implantation, hydrogels and nanoparticles (McCall et al, 2010). Among them, nanoparticle-based drug delivery may offer increased efficacy and reduced drug-associated side effects.…”

“…Certain physiological and anatomical features of the inner ear, such as the limited cochlear blood supply and the blood-inner ear barrier, can compromise the availability of systemic drug to target cells within the cochlea. Other disadvantages of systemic therapies are: (1) many drugs have short plasma half-lives; (2) if their molecular weight is high, parenteral resorption is impaired; and (3) there are large inter-individual variations due to variation in body metabolism (McCall et al, 2010).…”

Intratympanic Steroids in Sudden Sensorineural Hearing Loss: Myth or Magic?

“…Steroids may also be delivered to the round window via a microcatheter, a MicroWick [25], hydrogel applications, and nanoparticles. Transtympanic needle or tympanostomy tubes are the most frequently used [26]. The IT delivery route has additional benefit of avoiding the considerable side effects of further systemic steroid therapy.…”

Mathematical modeling for local trans-round window membrane drug transport in the inner ear

“…The blood-labyrinth barrier (BLB), which is physiologically similar to the blood-brain barrier (BBB), limits the concentration and size of molecules that can be transported from the blood circulation to the inner ear cell (McCall et al, 2010;Liu et al, 2013). There is an increasing interest in the use of topical applications for the treatment of inner ear disorders.…”

“…In contrast, intratympanic administration, which was introduced in clinics more than half a century ago, has proven to be an effective route for inner ear drug delivery with minimum damages (Duan & Chen, 2009). It is performed by the injection or perfusion of drugs into the middle ear with the aim of achieving drug diffusion through the round window membrane (RWM; McCall et al, 2010). The RWM is the only soft tissue structure located at the end of the scale tympani and separates the middle ear and the inner ear.…”