Development of a drug delivery system for the inner ear using poly(amino acid)-based nanoparticles

Abstract

Context: Local delivery systems for treatment of intractable inner ear disorders have been attempted by many investigators. Objective: To evaluate the permeability and safety of a drug delivery system for the inner ear using a poly(2-hydroxyethyl aspartamide) (PHEA) polymersome. Materials and methods: One-month-old male C57/BL6 mice were used. We administered the same amount of the fluorescent dye, Nile red, into the middle ear in two forms: loaded in PHEA polymersomes (NP group) or diluted in ethanol (NR group). At 1 day after administration, we harvested the cochlea and counted visible red particles in the tissues of cochlea under confocal microscopy and compared the groups. In a safety evaluation, 1 week after the same surgery, we conducted hearing tests and histological evaluations of the bulla and cochlea, and compared the results with those of the sham operation and negative control groups. Results: In terms of permeability, the number of red particles in the organ of Corti was increased significantly in the NP group, and three subjects in the NP group showed uptake of red particles in inner hair cells. However, there was no statistically significant difference in the observations in the lateral wall or modiolus. In safety tests, the NP and sham-operation groups showed decreased DPOAE responses and mildly swollen middle ear mucosa, compared with the negative control group, which was thought to be the result of postoperative changes. Conclusions: PHEA nanoparticles may have utility as a drug carrier into the inner ear in terms of both permeability and safety.