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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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In this graph the mean and SEM percentage of measurement of connective tissue growth in the scala tympani of all experimental groups for each cochlear turn from basal to apical are plotted.The comparison of tissue growth between the groups is illustrated by horizontal lines. Reference of the significance is marked by the thick bar. Highly significant differences were observed between tissue growth in the trauma group and groups receiving PBS or DEX by reservoir. No differences were measured between PBS or DEX treated groups even though a slightly increased connective tissue growth seems to be apparent in the PBS group compared to DEX treated animals. In cochleae implanted with a PBS releasing reservoir tissue growth could be measured from basal up to the 2nd middle turn whereas in the reservoir and DEX treated cochleae connective tissue formation was only visible in the lower and upper basal region. One-way ANOVA in combination with the Tukey post-test was used to compare means between groups: * = p<0.05; ** = p<0.01; *** = p<0.001.
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pone-0104564-g006: In this graph the mean and SEM percentage of measurement of connective tissue growth in the scala tympani of all experimental groups for each cochlear turn from basal to apical are plotted.The comparison of tissue growth between the groups is illustrated by horizontal lines. Reference of the significance is marked by the thick bar. Highly significant differences were observed between tissue growth in the trauma group and groups receiving PBS or DEX by reservoir. No differences were measured between PBS or DEX treated groups even though a slightly increased connective tissue growth seems to be apparent in the PBS group compared to DEX treated animals. In cochleae implanted with a PBS releasing reservoir tissue growth could be measured from basal up to the 2nd middle turn whereas in the reservoir and DEX treated cochleae connective tissue formation was only visible in the lower and upper basal region. One-way ANOVA in combination with the Tukey post-test was used to compare means between groups: * = p<0.05; ** = p<0.01; *** = p<0.001.

Mentions: The significantly most affected location of the cochlea are the basal turns when compared to more apical regions (p between <0.05 and <0.001; Fig. S9A–C). Fig. 6 and Fig. S9 illustrate the decrease of tissue growth from the basal to the apical parts of the cochleae. Comparisons of tissue growth within the turns of each experimental group are plotted in Fig. S9 A–C.


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)

In this graph the mean and SEM percentage of measurement of connective tissue growth in the scala tympani of all experimental groups for each cochlear turn from basal to apical are plotted.The comparison of tissue growth between the groups is illustrated by horizontal lines. Reference of the significance is marked by the thick bar. Highly significant differences were observed between tissue growth in the trauma group and groups receiving PBS or DEX by reservoir. No differences were measured between PBS or DEX treated groups even though a slightly increased connective tissue growth seems to be apparent in the PBS group compared to DEX treated animals. In cochleae implanted with a PBS releasing reservoir tissue growth could be measured from basal up to the 2nd middle turn whereas in the reservoir and DEX treated cochleae connective tissue formation was only visible in the lower and upper basal region. One-way ANOVA in combination with the Tukey post-test was used to compare means between groups: * = p<0.05; ** = p<0.01; *** = p<0.001.
© Copyright Policy
Related In: Results  -  Collection

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

pone-0104564-g006: In this graph the mean and SEM percentage of measurement of connective tissue growth in the scala tympani of all experimental groups for each cochlear turn from basal to apical are plotted.The comparison of tissue growth between the groups is illustrated by horizontal lines. Reference of the significance is marked by the thick bar. Highly significant differences were observed between tissue growth in the trauma group and groups receiving PBS or DEX by reservoir. No differences were measured between PBS or DEX treated groups even though a slightly increased connective tissue growth seems to be apparent in the PBS group compared to DEX treated animals. In cochleae implanted with a PBS releasing reservoir tissue growth could be measured from basal up to the 2nd middle turn whereas in the reservoir and DEX treated cochleae connective tissue formation was only visible in the lower and upper basal region. One-way ANOVA in combination with the Tukey post-test was used to compare means between groups: * = p<0.05; ** = p<0.01; *** = p<0.001.
Mentions: The significantly most affected location of the cochlea are the basal turns when compared to more apical regions (p between <0.05 and <0.001; Fig. S9A–C). Fig. 6 and Fig. S9 illustrate the decrease of tissue growth from the basal to the apical parts of the cochleae. Comparisons of tissue growth within the turns of each experimental group are plotted in Fig. S9 A–C.

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