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

Hütten M, Dhanasingh A, Hessler R, Stöver T, Esser KH, Möller M, Lenarz T, Jolly C, Groll J, Scheper V - PLoS ONE (2014)

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Otolaryngology, Hannover School of Medicine, Hannover, Germany; University of Veterinary Medicine Hannover, Foundation, Institute of Zoology, Hannover, Germany.

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.

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Related in: MedlinePlus

Image of a hydrogel reservoir with one end closed by a silicone septum for fluid injections (right end), while the other end is open in order to release the drug into the area to be addressed (left end) and calculation of the amount of drug inside the hydrogel filled tube.Drug release from this arrangement is shown in the diagram. The data points result from nine experiments from three different NCO-sP(EO-stat-PO) batches, each of them used for the preparation of three release setups.
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pone-0104564-g001: Image of a hydrogel reservoir with one end closed by a silicone septum for fluid injections (right end), while the other end is open in order to release the drug into the area to be addressed (left end) and calculation of the amount of drug inside the hydrogel filled tube.Drug release from this arrangement is shown in the diagram. The data points result from nine experiments from three different NCO-sP(EO-stat-PO) batches, each of them used for the preparation of three release setups.

Mentions: In this configuration, the release of drug may logically occur only through the open end of the silicone tube. The walls of the silicone tube will restrict the hydrogel to swell to its full equilibrium state, hence at every point of time the hydrogel will exert a swelling force against the inner wall of the silicone tube by which the hydrogel adjusts tightly to the inside wall of the silicone tube. The exact dimension of the silicone tube reservoir with the amount of drug molecule inside the hydrogel and the cumulative release profile is shown in Fig. 1. Reproducibility of the hydrogel packing inside the silicone tube reservoir and the kinetics of the drug release were performed with three batches of separately prepared DEX loaded hydrogels with each of the batches inserted in three different tubes. Although the release of the drug happens by diffusion process, the geometrical constraint result in a time of about 900 hours or 38 days until DEX is quantitatively released. Interestingly, there was only negligible release in the first 50 hours. This may be explained by the initial diffusion of water inside the gel such that maximal water content in the tube is reached allowing the diffusion controlled release to start.


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

Hütten M, Dhanasingh A, Hessler R, Stöver T, Esser KH, Möller M, Lenarz T, Jolly C, Groll J, Scheper V - PLoS ONE (2014)

Image of a hydrogel reservoir with one end closed by a silicone septum for fluid injections (right end), while the other end is open in order to release the drug into the area to be addressed (left end) and calculation of the amount of drug inside the hydrogel filled tube.Drug release from this arrangement is shown in the diagram. The data points result from nine experiments from three different NCO-sP(EO-stat-PO) batches, each of them used for the preparation of three release setups.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4126769&req=5

pone-0104564-g001: Image of a hydrogel reservoir with one end closed by a silicone septum for fluid injections (right end), while the other end is open in order to release the drug into the area to be addressed (left end) and calculation of the amount of drug inside the hydrogel filled tube.Drug release from this arrangement is shown in the diagram. The data points result from nine experiments from three different NCO-sP(EO-stat-PO) batches, each of them used for the preparation of three release setups.
Mentions: In this configuration, the release of drug may logically occur only through the open end of the silicone tube. The walls of the silicone tube will restrict the hydrogel to swell to its full equilibrium state, hence at every point of time the hydrogel will exert a swelling force against the inner wall of the silicone tube by which the hydrogel adjusts tightly to the inside wall of the silicone tube. The exact dimension of the silicone tube reservoir with the amount of drug molecule inside the hydrogel and the cumulative release profile is shown in Fig. 1. Reproducibility of the hydrogel packing inside the silicone tube reservoir and the kinetics of the drug release were performed with three batches of separately prepared DEX loaded hydrogels with each of the batches inserted in three different tubes. Although the release of the drug happens by diffusion process, the geometrical constraint result in a time of about 900 hours or 38 days until DEX is quantitatively released. Interestingly, there was only negligible release in the first 50 hours. This may be explained by the initial diffusion of water inside the gel such that maximal water content in the tube is reached allowing the diffusion controlled release to start.

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Otolaryngology, Hannover School of Medicine, Hannover, Germany; University of Veterinary Medicine Hannover, Foundation, Institute of Zoology, Hannover, Germany.

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.

Show MeSH
Related in: MedlinePlus