Inner ear delivery: Challenges and opportunities

Abstract

Objectives The treatment of inner ear disorders remains challenging due to anatomic barriers intrinsic to the bony labyrinth. The purpose of this review is to highlight recent advances and strategies for overcoming these barriers and to discuss promising future avenues for investigation. Data Sources The databases used were PubMed, EMBASE, and Web of Science. Results Although some studies aimed to improve systemic delivery using nanoparticle systems, the majority enhanced local delivery using hydrogels, nanoparticles, and microneedles. Developments in direct intracochlear delivery include intracochlear injection and intracochlear implants. Conclusions In the absence of a systemic drug that targets only the inner ear, the best alternative is local delivery that harnesses a combination of new strategies to overcome anatomic barriers. The combination of microneedle technology with hydrogel and nanoparticle delivery is a promising area for future investigation. Level of Evidence NA

Nanoparticles for the Treatment of Inner Ear Infections

“…Inner ear infections are challenging to treat due to their isolated location. Placed in the temporal bone, the inner ear is protected by many anatomical and physiological barriers, which hinder therapeutics’ delivery ( Figure 2 ) [ 14 , 51 , 52 , 53 , 54 , 55 , 56 ].…”

“…Superparamagnetic iron oxide nanoparticles (SPIONs) are another promising strategy as they can be magnetically guided across the round window and precisely reach the targeted inner ear structures [ 13 , 56 , 59 ]. Moreover, their relatively simple synthesis, low toxicity, intrinsic antimicrobial activity, and functionalization ability are very important properties for designing effective biocompatible nanoplatforms [ 98 ].…”

“…SPIONs cannot encapsulate any substance, but they can be loaded into polymeric nanoparticles or coated with the needed drug. For inner ear drug delivery, SPIONs have been tested in combination with PLGA, chitosan, silica, and dextran [ 13 , 51 , 56 ]. Such nanocomposites can significantly enhance antibiotics’ activity against both Gram-positive and Gram-negative bacteria, being a helpful tool in treating multi-drug resistant pathogen strains infections [ 99 , 100 , 101 ].…”

Understanding and treating paediatric hearing impairment

“…Intracochlear injection targeting scala tympani via the round window membrane is the most commonly used route of administration in current preclinical studies. While being more invasive than the above approaches with higher risk of further hearing deterioration, the method offers important advantages such more consistently reaching sufficient target concentrations and local action of the therapeutics [87] . Moreover, injecting AAV9-PHP.B successfully and efficiently transduced hair cells by delivery via a round window membrane approach in non-human primates [88] .…”

“…Moreover, injecting AAV9-PHP.B successfully and efficiently transduced hair cells by delivery via a round window membrane approach in non-human primates [88] . Intracochlear delivery such as cochleostomy, perforating the stapes footplate, fenestration of the posterior semicircular canal (canalostomy) – possibly in combination with drug application catheters in scala tympani [87] – are more invasive with a higher risk of hearing loss. Direct administration into the cochlear modiolus has been successfully used for grafting otic neural progenitor cells [89] and AAV-mediated optogenetic manipulation of SGNs [55].…”