Limits...
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.

Show MeSH

Related in: MedlinePlus

Distribution of fibrosis regarding subjective ranking for all inner ear turns and all experimental groups.In all groups the highest extend of connective tissue growth was detected in the basal turns. Fibroblast growth in more apical turns was only detected in the trauma group and did not take place in reservoir groups at all. Significant differences between the groups were detected (plotted above the SEM bars: * = p<0.05, *** = p<0.001; reference of the significance is marked by the thick bar) and were most prominent in the lower basal turns (p<0.001). Even though there seems to be a tendency of increased tissue formation in the PBS group compared to the DEX group there is no statistical relevance detectable using One-way ANOVA in combination with the Tukey post-test to compare the means between groups.
© Copyright Policy
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4126769&req=5

pone-0104564-g005: Distribution of fibrosis regarding subjective ranking for all inner ear turns and all experimental groups.In all groups the highest extend of connective tissue growth was detected in the basal turns. Fibroblast growth in more apical turns was only detected in the trauma group and did not take place in reservoir groups at all. Significant differences between the groups were detected (plotted above the SEM bars: * = p<0.05, *** = p<0.001; reference of the significance is marked by the thick bar) and were most prominent in the lower basal turns (p<0.001). Even though there seems to be a tendency of increased tissue formation in the PBS group compared to the DEX group there is no statistical relevance detectable using One-way ANOVA in combination with the Tukey post-test to compare the means between groups.

Mentions: In all experimental groups tissue growth was significantly worse in the basal half turns of the cochleae (Fig. 5 and S8) compared to the apical region or the middle turns (p<0.001) (Fig. S8). Concerning this characteristic, all groups achieved similar tendencies. In the trauma group basal turns (lower and upper basal turn) achieved a ranking score of 2.04±0.25. Middle turns a score of 0.42±0.19 and apical turns a value of 0.08±0.08 (p<0.001; Fig S8A). Basal turns of the reservoir + PBS group showed tissue growth with a ranking score of 1.45±0.16 (Fig. S8B). Middle turns of 0.09±0.05 and basal turns of the reservoir + DEX group had a score of 0.88±0.11, while middle turns received a score of 0.0004±0.0004 (Fig. S8C). Both of the reservoir groups exhibited no fibrotic tissue response in the apical turns Comparison of fibrotic tissue reaction in middle and apical turns did not show any significant differences (Fig. S8A–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)

Distribution of fibrosis regarding subjective ranking for all inner ear turns and all experimental groups.In all groups the highest extend of connective tissue growth was detected in the basal turns. Fibroblast growth in more apical turns was only detected in the trauma group and did not take place in reservoir groups at all. Significant differences between the groups were detected (plotted above the SEM bars: * = p<0.05, *** = p<0.001; reference of the significance is marked by the thick bar) and were most prominent in the lower basal turns (p<0.001). Even though there seems to be a tendency of increased tissue formation in the PBS group compared to the DEX group there is no statistical relevance detectable using One-way ANOVA in combination with the Tukey post-test to compare the means between groups.
© Copyright Policy
Related In: Results  -  Collection

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

pone-0104564-g005: Distribution of fibrosis regarding subjective ranking for all inner ear turns and all experimental groups.In all groups the highest extend of connective tissue growth was detected in the basal turns. Fibroblast growth in more apical turns was only detected in the trauma group and did not take place in reservoir groups at all. Significant differences between the groups were detected (plotted above the SEM bars: * = p<0.05, *** = p<0.001; reference of the significance is marked by the thick bar) and were most prominent in the lower basal turns (p<0.001). Even though there seems to be a tendency of increased tissue formation in the PBS group compared to the DEX group there is no statistical relevance detectable using One-way ANOVA in combination with the Tukey post-test to compare the means between groups.
Mentions: In all experimental groups tissue growth was significantly worse in the basal half turns of the cochleae (Fig. 5 and S8) compared to the apical region or the middle turns (p<0.001) (Fig. S8). Concerning this characteristic, all groups achieved similar tendencies. In the trauma group basal turns (lower and upper basal turn) achieved a ranking score of 2.04±0.25. Middle turns a score of 0.42±0.19 and apical turns a value of 0.08±0.08 (p<0.001; Fig S8A). Basal turns of the reservoir + PBS group showed tissue growth with a ranking score of 1.45±0.16 (Fig. S8B). Middle turns of 0.09±0.05 and basal turns of the reservoir + DEX group had a score of 0.88±0.11, while middle turns received a score of 0.0004±0.0004 (Fig. S8C). Both of the reservoir groups exhibited no fibrotic tissue response in the apical turns Comparison of fibrotic tissue reaction in middle and apical turns did not show any significant differences (Fig. S8A–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