The University of Southampton
University of Southampton Institutional Repository

Minimally invasive drug delivery to the cochlea through application of nanoparticles to the round window membrane

Minimally invasive drug delivery to the cochlea through application of nanoparticles to the round window membrane
Minimally invasive drug delivery to the cochlea through application of nanoparticles to the round window membrane
Direct drug delivery to the cochlea is associated with the risk of irreversible damage to the ear. In this study liposome and polymersome nanoparticles (NPs), both formed from amphiphilic molecules (lipids in liposomes, block copolymers in polymersomes), were tested as potential tools for drug delivery to the cochlea through application onto the round window membrane (RWM) in adult mice (strain C3H). One day after RWM application both types of NPs labelled with fluorescent markers were identified in the spiral ganglion in all cochlear turns without producing any distinct morphological or functional damage to the inner ear. NPs were detected, although to a lesser extent, in the organ of Corti and the lateral wall. The potential of liposome and polymersome NPs as therapeutic delivery systems into the cochlea via the RWM was evaluated using disulfiram, a neurotoxic agent as a model payload. Disulfiram-loaded NP delivery resulted in significant decrease in the number of spiral ganglion cells starting two days post-application, with associated pronounced hearing loss reaching 20-35 dB two weeks post-application as assessed through auditory brainstem responses. No changes in hair cell morphology and function (as assessed by recording of otoacoustic emissions) were detected after disulfiram-loaded NP application. No effects were observed in controls where solution of free disulfiram was similarly administered. The results demonstrate that polymersome and liposome NPs are capable of carrying a payload into the inner ear that elicits a biological effect, with consequences measurable by a functional readout.
1743-5889
1339-1354
Buckiova, Daniela
dffdfc60-bb5f-434c-9974-1dc409f268c9
Ranjan, Sanjeev
60a1d774-3150-42b8-ae6c-2c35e9d42521
Newman, Tracey A.
322290cb-2e9c-445d-a047-00b1bea39a25
Johnston, Alexander H.
b3325b84-67c4-4d9c-ba97-57f2fdf017ba
Sood, Rohit
de0babc4-1ec1-4035-b653-812b8e2dd9c3
Kinnunen, Paavo K.J.
f3ba8e95-a4e5-498f-958e-d99c7115aae8
Popelář, Jiří
33fa2017-d2ed-473f-b165-cf565cfb4836
Chumak, Tetyana
755ed0c7-ae3b-4bdb-bad9-57bd3712a0ed
Syka, Josef
7883fbaf-be8b-4a51-afae-5f1016880fbe
Buckiova, Daniela
dffdfc60-bb5f-434c-9974-1dc409f268c9
Ranjan, Sanjeev
60a1d774-3150-42b8-ae6c-2c35e9d42521
Newman, Tracey A.
322290cb-2e9c-445d-a047-00b1bea39a25
Johnston, Alexander H.
b3325b84-67c4-4d9c-ba97-57f2fdf017ba
Sood, Rohit
de0babc4-1ec1-4035-b653-812b8e2dd9c3
Kinnunen, Paavo K.J.
f3ba8e95-a4e5-498f-958e-d99c7115aae8
Popelář, Jiří
33fa2017-d2ed-473f-b165-cf565cfb4836
Chumak, Tetyana
755ed0c7-ae3b-4bdb-bad9-57bd3712a0ed
Syka, Josef
7883fbaf-be8b-4a51-afae-5f1016880fbe

Buckiova, Daniela, Ranjan, Sanjeev, Newman, Tracey A., Johnston, Alexander H., Sood, Rohit, Kinnunen, Paavo K.J., Popelář, Jiří, Chumak, Tetyana and Syka, Josef (2012) Minimally invasive drug delivery to the cochlea through application of nanoparticles to the round window membrane. Nanomedicine, 7 (9), 1339-1354. (doi:10.2217/nnm.12.5). (PMID:22475648)

Record type: Article

Abstract

Direct drug delivery to the cochlea is associated with the risk of irreversible damage to the ear. In this study liposome and polymersome nanoparticles (NPs), both formed from amphiphilic molecules (lipids in liposomes, block copolymers in polymersomes), were tested as potential tools for drug delivery to the cochlea through application onto the round window membrane (RWM) in adult mice (strain C3H). One day after RWM application both types of NPs labelled with fluorescent markers were identified in the spiral ganglion in all cochlear turns without producing any distinct morphological or functional damage to the inner ear. NPs were detected, although to a lesser extent, in the organ of Corti and the lateral wall. The potential of liposome and polymersome NPs as therapeutic delivery systems into the cochlea via the RWM was evaluated using disulfiram, a neurotoxic agent as a model payload. Disulfiram-loaded NP delivery resulted in significant decrease in the number of spiral ganglion cells starting two days post-application, with associated pronounced hearing loss reaching 20-35 dB two weeks post-application as assessed through auditory brainstem responses. No changes in hair cell morphology and function (as assessed by recording of otoacoustic emissions) were detected after disulfiram-loaded NP application. No effects were observed in controls where solution of free disulfiram was similarly administered. The results demonstrate that polymersome and liposome NPs are capable of carrying a payload into the inner ear that elicits a biological effect, with consequences measurable by a functional readout.

PDF
207167.pdf - Version of Record
Restricted to Repository staff only
Request a copy

More information

e-pub ahead of print date: 4 April 2012
Organisations: Faculty of Medicine

Identifiers

Local EPrints ID: 207167
URI: https://eprints.soton.ac.uk/id/eprint/207167
ISSN: 1743-5889
PURE UUID: c04740da-be21-4297-b52b-a6b537f90d1c
ORCID for Tracey A. Newman: ORCID iD orcid.org/0000-0002-3727-9258

Catalogue record

Date deposited: 11 Jan 2012 11:43
Last modified: 10 Jan 2019 01:37

Export record

Altmetrics

Contributors

Author: Daniela Buckiova
Author: Sanjeev Ranjan
Author: Alexander H. Johnston
Author: Rohit Sood
Author: Paavo K.J. Kinnunen
Author: Jiří Popelář
Author: Tetyana Chumak
Author: Josef Syka

University divisions

Download statistics

Downloads from ePrints over the past year. Other digital versions may also be available to download e.g. from the publisher's website.

View more statistics

Atom RSS 1.0 RSS 2.0

Contact ePrints Soton: eprints@soton.ac.uk

ePrints Soton supports OAI 2.0 with a base URL of https://eprints.soton.ac.uk/cgi/oai2

This repository has been built using EPrints software, developed at the University of Southampton, but available to everyone to use.

We use cookies to ensure that we give you the best experience on our website. If you continue without changing your settings, we will assume that you are happy to receive cookies on the University of Southampton website.

×