title: Distribution of lipid nanocapsules in different cochlear cell populations after round window membrane permeation.
abstract: Hearing loss is a major public health problem, and its treatment with traditional therapy strategies is often unsuccessful due to limited drug access deep in the temporal bone. Multifunctional nanoparticles that are targeted to specified cell populations, biodegradable, traceable in vivo, and equipped with controlled drug/gene release may resolve this problem. We developed lipid core nanocapsules (LNCs) with sizes below 50 nm. The aim of the present study is to evaluate the ability of the LNCs to pass through the round window membrane and reach inner ear targets. FITC was incorporated as a tag for the LNCs and Nile Red was encapsulated inside the oily core to assess the integrity of the LNCs. The capability of LNCs to pass through the round window membrane and the distribution of the LNCs inside the inner ear were evaluated in rats via confocal microscopy in combination with image analysis using ImageJ. After round window membrane administration, LNCs reached the spiral ganglion cells, nerve fibers, and spiral ligament fibrocytes within 30 min. The paracellular pathway was the main approach for LNC penetration of the round window membrane. LNCs can also reach the vestibule, middle ear mucosa, and the adjacent artery. Nuclear localization was detected in the spiral ganglion, though infrequently. These results suggest that LNCs are potential vectors for drug delivery into the spiral ganglion cells, nerve fibers, hair cells, and spiral ligament.
authors.affiliation: Department of Otolaryngology, University of Tampere, School of Medicine, 33520 Tampere, Finland. Jing.Zou@uta.fi
authors.forename: Jing
authors.initials: J
authors.lastname: Zou
authors.forename: Patrick
authors.initials: P
authors.lastname: Saulnier
authors.forename: Thomas
authors.initials: T
authors.lastname: Perrier
authors.forename: Ya
authors.initials: Y
authors.lastname: Zhang
authors.forename: Tommi
authors.initials: T
authors.lastname: Manninen
authors.forename: Esko
authors.initials: E
authors.lastname: Toppila
authors.forename: Ilmari
authors.initials: I
authors.lastname: Pyykkö
mesh_terms: D000818:Animals; D003051:Cochlea / Q000166:cytology* / Q000378:metabolism; D004337:Drug Carriers / Q000737:chemistry* / Q000493:pharmacokinetics; D016503:Drug Delivery Systems; D007758:Ear, Inner; D008055:Lipids / Q000493:pharmacokinetics*; D018613:Microscopy, Confocal; D053769:Nanocapsules / Q000737:chemistry* / Q000627:therapeutic use; D051381:Rats; D014018:Tissue Distribution
chemical_list: D004337:Drug Carriers; D008055:Lipids; D053769:Nanocapsules