title: Inner ear biocompatibility of lipid nanocapsules after round window membrane application.
abstract: Nanoparticle-mediated drug delivery represents the future in terms of treating inner ear diseases. Lipid core nanocapsules (LNCs), 50 nm in size, were shown to pass though the round window membrane (RWM) and reached the spiral ganglion cells and nerve fibers, among other cell types in the inner ear. The present study aimed to evaluate the toxicity of the LNCs in vitro and in vivo, utilizing intact round window membrane delivery in rats. The primary cochlear cells and mouse fibroblast cells treated with LNCs displayed dosage dependant toxicity. In vivo study showed that administration of LNCs did not cause hearing loss, nanoparticle application-related cell death, or morphological changes in the inner ear, at up to 28 days of observation. The cochlear neural elements, such as synaptophysin, ribbon synapses, and S-100, were not affected by the administration of LNCs. However, expression of neurofilament-200 decreased in SGCs and in cochlear nerve in osseous spiral lamina canal after LNC delivery, a phenomenon that requires further investigation. LNCs are potential vectors for the delivery of drugs to the inner ear.
authors.affiliation: Department of Otolaryngology, University of Tampere, Medical School, FM1, 3rd Floor, Biokatu 6, 33520 Tampere, Finland.
authors.forename: Ya
authors.initials: Y
authors.lastname: Zhang
authors.forename: Weikai
authors.initials: W
authors.lastname: Zhang
authors.forename: Marian
authors.initials: M
authors.lastname: Löbler
authors.forename: Klaus-Peter
authors.initials: KP
authors.lastname: Schmitz
authors.forename: Patrick
authors.initials: P
authors.lastname: Saulnier
authors.forename: Thomas
authors.initials: T
authors.lastname: Perrier
authors.forename: Ilmari
authors.initials: I
authors.lastname: Pyykkö
authors.forename: Jing
authors.initials: J
authors.lastname: Zou
mesh_terms: D000161:Acoustic Stimulation; D000818:Animals; D000831:Animals, Newborn; D001309:Auditory Threshold / Q000187:drug effects; D001672:Biocompatible Materials; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D002626:Chemistry, Pharmaceutical; D004305:Dose-Response Relationship, Drug; D004337:Drug Carriers; D004339:Drug Compounding; D016057:Evoked Potentials, Auditory, Brain Stem / Q000187:drug effects; D005347:Fibroblasts / Q000187:drug effects / Q000473:pathology; D020128:Inhibitory Concentration 50; D008055:Lipids / Q000737:chemistry / Q000633:toxicity*; D008297:Male; D051379:Mice; D053769:Nanocapsules; D036103:Nanotechnology; D037121:Plant Lectins / Q000737:chemistry / Q000633:toxicity; D011092:Polyethylene Glycols / Q000737:chemistry / Q000633:toxicity; D051381:Rats; D017207:Rats, Sprague-Dawley; D012405:Round Window, Ear / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D030262:Soybean Proteins / Q000737:chemistry / Q000633:toxicity; D013228:Stearates / Q000737:chemistry / Q000633:toxicity; D013229:Stearic Acids / Q000737:chemistry / Q000633:toxicity; D013678:Technology, Pharmaceutical / Q000379:methods; D014280:Triglycerides / Q000737:chemistry / Q000633:toxicity; D010835:Phytohemagglutinins
chemical_list: D001672:Biocompatible Materials; D004337:Drug Carriers; D008055:Lipids; D053769:Nanocapsules; D037121:Plant Lectins; D011092:Polyethylene Glycols; D030262:Soybean Proteins; D013228:Stearates; D013229:Stearic Acids; D014280:Triglycerides; C542236:labrafac WL 1349; C466738:polyethylene glycol 660 12-hydroxy stearate; C028824:soybean lectin; D010835:Phytohemagglutinins; C067028:Solutol HS 15