title: Use of the biodegradable polymer chitosan as a vehicle for applying drugs to the inner ear.
abstract: Development of efficient local delivery systems for the auditory organ has an important role in clinical practice for the management of inner ear disorders using pharmacological means. Chitosan, a biodegradable polymer, is a good drug carrier with bioadhesive properties. The aim of this study was to investigate the feasibility of using chitosan to deliver drugs to the inner ear across the round window membrane (RWM). Three structurally different chitosans loaded with a tracer drug, neomycin, were injected into the middle ear cavity of albino guinea pigs (n=35). After 7 days the effect of chitosans and neomycin was compared among the treatment groups. The hearing organ was analysed for hair cell loss and the RWM evaluated in term of thickness. All tested chitosan formulations successfully released the loaded neomycin which then diffused across the RWM, and exerted ototoxic effect on the cochlear hair cells in a degree depending on the concentrations used. Chitosans per se had no noxious effect on the cochlear hair cells. It is concluded that the chitosans, and especially glycosylated derivative, are safe and effective carriers for inner ear therapy.
authors.affiliation: Center for Hearing and Communication Research, Department of Clinical Neuroscience, Karolinska Institutet, SE-171 76 Stockholm, Sweden. amanj.saber@ki.se
authors.forename: Amanj
authors.initials: A
authors.lastname: Saber
authors.forename: Sabina P
authors.initials: SP
authors.lastname: Strand
authors.forename: Mats
authors.initials: M
authors.lastname: Ulfendahl
mesh_terms: D000818:Animals; D001672:Biocompatible Materials / Q000008:administration & dosage* / Q000737:chemistry; D048271:Chitosan / Q000008:administration & dosage* / Q000031:analogs & derivatives / Q000737:chemistry; D004305:Dose-Response Relationship, Drug; D004337:Drug Carriers / Q000008:administration & dosage* / Q000138:chemical synthesis; D007758:Ear, Inner / Q000187:drug effects*; D006168:Guinea Pigs; D006199:Hair Cells, Auditory, Inner / Q000187:drug effects / Q000473:pathology; D007322:Instillation, Drug; D009355:Neomycin / Q000008:administration & dosage / Q000009:adverse effects; D014677:Pharmaceutical Vehicles / Q000008:administration & dosage*; D012405:Round Window, Ear / Q000187:drug effects / Q000473:pathology
chemical_list: D001672:Biocompatible Materials; D004337:Drug Carriers; D014677:Pharmaceutical Vehicles; D048271:Chitosan; D009355:Neomycin