Disposition of Nanoparticle-Based Delivery System via Inner Ear Administration

Gang      Chen; Xiao      Zhang; Fan      Yang; Lei      Mu

Abstract

The inner ear is difficult to access by conventional systemic drug delivery due to formidable physiological and anatomic barriers. There is an increasing interest in the treatment of inner ear disorders by topical application of drugs to the inner ear. One of the most important issues to overcome before full clinical application is the development of smart delivery systems for drugs to the target sites and controlled release in the inner ear. This is an area where nanoparticles will play an extremely important role. These submicron particles have exhibited improved biocompatibility, in vivo stability, target specificity, and cell/tissue uptake and internalization of the encapsulated therapeutic agents, leading to a decrease in the dose required and a decrease in side effects. This unique combination of properties makes nanoparticles a novel delivery device, which fulfils the requirements for inner ear application. This review will summarize recent findings and applications of various nanoparticle-based systems like poly (D, L-lactic/glycolic acid) nanoparticles, magnetic nanoparticles, lipid nanoparticles, liposomes, polymersomes, hydroxyapatite nanoparticles, and silica nanoparticles in the field of inner ear drug delivery. Moreover, the review will provide an insight into the future strategies of nanoparticle-based cochlear drug delivery. In conjunction, physiological considerations related to inner ear administration will be highlighted. The routes and applications for local inner- ear drug delivery will also be mentioned. In closing, this review will give an overview of the potential future development in inner ear administration with nanoparticles.

Keywords: Nanoparticles, cochlea, local drug delivery, intratympanic administration, round window membrane, perilymph, anatomic barri-ers, therapeutic agents, lipid nanoparticles, liposomes, polymersomes, hydroxyapatite nanoparticles, blood-inner ear barrier, otologic treatments, tympanic membrane, round window, scala vestibuli, cerebrospinal fluid, microhomeostasis, blood capillaries, scala tympan, micropinocytic vesicles, concentration, configuration, liposolubility, hyaluronic acid, osmotic effects, dimethylsulfoxide, tympani, sensorineural, Rhodamine, maghemite, magnetite, Rosenthal's canal, spiral ganglion, tunnel fibers, Corti's liquid, intratympanic injection, green fluorescent protein, Reissner's membrane, pheochromocytoma cells