Developments in Bio-Inspired Nanomaterials for Therapeutic Delivery to Treat Hearing Loss

Abstract

Sensorineural hearing loss affects millions of people worldwide and is a growing concern in the aging population. Treatment using aminoglycoside antibiotics for infection and exposure to loud sounds contribute to the degeneration of cochlear hair cells and spiral ganglion neurons. Cell loss impacts cochlear function and causes hearing loss in ∼ 15% of adult Americans (∼36 million). The number of individuals with hearing loss will likely grow with increasing lifespans. Current prosthesis such as hearing aids and cochlear implants can ameliorate hearing loss. However, hearing aids are ineffective if hair cells or spiral ganglion neurons are severely damaged, and cochlear implants are ineffective without properly functioning spiral ganglion neurons. As such, strategies that alleviate hearing loss by preventing degeneration or promoting cell replacement are urgently needed. Despite showing great promise from in vitro studies, the complexity and delicate nature of the inner ear poses a huge challenge for delivering therapeutics. To mitigate risks and complications associated with surgery, new technologies and methodologies have emerged for efficient delivery of therapeutics. We will focus on biomaterials that allow controlled and local drug delivery into the inner ear. The rapid development of microsurgical techniques in conjunction with novel bio- and nanomaterials for sustained drug delivery appears bright for hearing loss treatment.

A Review on Recent Advancement on Age-Related Hearing Loss: The Applications of Nanotechnology, Drug Pharmacology, and Biotechnology

“…Clearance of the middle ear via the Eustachian tube is another concept to consider when designing an inner ear drug delivery system. This consistent elimination of the contents of the middle ear can result in the necessity for repeated injections to achieve therapeutic levels, prompting research efforts into controlled drug release and the retainment of drug carriers in the middle ear [ 95 , 112 , 113 , 114 , 115 ].…”

“…When designing a nanocarrier delivery system, the excipients and method of formulation for the carrier determine the physiochemical characteristics of the finalised capsule [ 126 , 135 , 136 , 137 , 138 ]. Several reviews have summarised the benefits of nanocarriers in applications to inner ear delivery, highlighting improvements in biodistributions and availability, RWM transportability, otoprotective effects, and the reduction in the targeted effect in the outer hair cells and stria vascularis [ 95 , 113 , 139 ]. The prospect of microencapsulation for inner ear drug delivery has not yet been explored, but due to its larger size, would not seem to be a viable option for RWM transport.…”

Nanomedicine Approaches to Negotiate Local Biobarriers for Topical Drug Delivery

“…Drainage of drugs through the cochlear aqueduct from the inner ear to the cranial fossa is also responsible for decreasing residence time. [ 296–298 ] Chitosan glycerophosphate (CGP) hydrogel matrix can help with ear drug delivery due to its mucoadhesion and ability to load a broad range of drugs. CGP hydrogels can deliver dexamethasone to the inner ear in mouse.…”

“…The round window membrane is a biobarrier that regulates access of drugs to the cochlea. [296,297] Indeed, intratympanic injections (IT) are the most common treatment for local drug administration to inner ear. Yet IT injection to the middle ear for treating inner ear pathologies suffers from low efficacy due to the poor stability of labile drugs in the degrading middle ear environment and their low biodistribution to the inner ear due to the combined rapid drainage through the Eustachian tube and limited permeability across the RWM.…”

Determination of the Round Window Niche Anatomy Using Cone Beam Computed Tomography Imaging as Preparatory Work for Individualized Drug-Releasing Implants

“…Drug delivery would be sustained if the drug remained on the RWM which is, in part, already achieved by gel-matrix based RWM delivery. However the matrix based delivery is not yet controlled in terms of matrix size and drug load [6,13,14].…”