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  • In vitro and in vivo evaluation of a hydrogel reservoir as a continuous drug delivery system for inner ear treatment.

In vitro and in vivo evaluation of a hydrogel reservoir as a continuous drug delivery system for inner ear treatment.

PloS one (2014-08-12)
Mareike Hütten, Anandhan Dhanasingh, Roland Hessler, Timo Stöver, Karl-Heinz Esser, Martin Möller, Thomas Lenarz, Claude Jolly, Jürgen Groll, Verena Scheper
ABSTRACT

Fibrous tissue growth and loss of residual hearing after cochlear implantation can be reduced by application of the glucocorticoid dexamethasone-21-phosphate-disodium-salt (DEX). To date, sustained delivery of this agent to the cochlea using a number of pharmaceutical technologies has not been entirely successful. In this study we examine a novel way of continuous local drug application into the inner ear using a refillable hydrogel functionalized silicone reservoir. A PEG-based hydrogel made of reactive NCO-sP(EO-stat-PO) prepolymers was evaluated as a drug conveying and delivery system in vitro and in vivo. Encapsulating the free form hydrogel into a silicone tube with a small opening for the drug diffusion resulted in delayed drug release but unaffected diffusion of DEX through the gel compared to the free form hydrogel. Additionally, controlled DEX release over several weeks could be demonstrated using the hydrogel filled reservoir. Using a guinea-pig cochlear trauma model the reservoir delivery of DEX significantly protected residual hearing and reduced fibrosis. As well as being used as a device in its own right or in combination with cochlear implants, the hydrogel-filled reservoir represents a new drug delivery system that feasibly could be replenished with therapeutic agents to provide sustained treatment of the inner ear.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Dexamethasone 21-phosphate disodium salt, ≥98%
Sigma-Aldrich
Lithium sulfate, purum p.a., ≥98.0% (T)
Sigma-Aldrich
o-Toluidine, ≥99%
Sigma-Aldrich
o-Toluidine, purum p.a., ≥99.5% (GC)
Sigma-Aldrich
Lithium sulfate, ≥99.99% trace metals basis
Sigma-Aldrich
o-Toluidine, 98%
Sigma-Aldrich
Sodium phosphate, 96%
Sigma-Aldrich
Lithium sulfate, ≥98.5% (titration)
Sigma-Aldrich
Lithium-7Li2 sulfate, 99 atom % 7Li
Dexamethasone sodium phosphate for peak identification, European Pharmacopoeia (EP) Reference Standard
Dexamethasone sodium phosphate, European Pharmacopoeia (EP) Reference Standard