Round window membrane and delivery of biologically active agents into the cochlea

摘要: Establishing efficient methods for local administration of drugs to the inner ear has great clinical relevance management disorders. However, route remains a critical issue. The most feasible approach non invasive drug delivery is application medication middle cavity on promise that it will diffuse through thin round window membrane (RWM) separating from cavity. Gene therapy represents promising future in otology and offers an exciting therapeutic alternative as could be used prevention or cochlear Also gene approach, RWM seems route. Exploring characterizing thus fundamentally important area research development treatment objectives thesis were evaluate efficacy two delivering vehicles ear, sodium hyaluronate (HYA) chitosans, which can applied cochlea. Ultimate aim establish system transfection ear. HYA chitosans loaded with ototoxic neomycin tracer release have been instilled into guinea pigs. Effects hair cells evaluated after single instillation (day 7 28), saline solution 7). hearing organ was analysed cell loss thickness ultrastructural properties by light transmission electron microscopy. vitro efficiency chitosan tested exposing organotypic cultures Corti, prepared postnatal day 2 rats, carrying plasmid DNA (pDNA). vivo at one seven days infusing chitosan/pDNA polyplexes use osmotic pumps cochlea adult Tissue analysis made immunohistochemsitry RT-PCR. especially glycosylated derivative, are safe transport RWM. Both successfully released neomycin, exerted toxic effects degree depending concentrations used. per se had no noxious effect but they provoked comparable morphology returned normal 4 weeks exposure HYA. Chitosan carrier transfection, associated inconsistent . importance portal disorders highlighted this focusing vehicles, biologically active agents difficulties variability applying substances explored. results add new knowledge concerning mechanisms passage may help us better understand role problems diseases.