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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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Graphed t-test results of tissue growth ranking (A) and measurement (B) for the whole cochlea length.Using both evaluation methods the tissue growth in the trauma group was significantly increased compared to the reservoir and DEX group with a p value <0.001. When applying the ranking score the difference between reservoir + PBS and trauma or reservoir + DEX was significant with p<0.05 (A). Comparing the tissue growth of the reservoir + PBS group with those of the trauma group or the DEX group using the measuring method, the p value is <0.001 (PBS vs. trauma) and <0.05 (PBS vs. DEX). Error bars: SEM. * = p<0.05, *** = p<0.001.
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pone-0104564-g004: Graphed t-test results of tissue growth ranking (A) and measurement (B) for the whole cochlea length.Using both evaluation methods the tissue growth in the trauma group was significantly increased compared to the reservoir and DEX group with a p value <0.001. When applying the ranking score the difference between reservoir + PBS and trauma or reservoir + DEX was significant with p<0.05 (A). Comparing the tissue growth of the reservoir + PBS group with those of the trauma group or the DEX group using the measuring method, the p value is <0.001 (PBS vs. trauma) and <0.05 (PBS vs. DEX). Error bars: SEM. * = p<0.05, *** = p<0.001.

Mentions: Using student's t-test the evaluation of fibrotic tissue response in the whole cochlea by use of a subjective scoring system revealed significant differences between the three experimental groups (Fig. 4A). The trauma group suffered from a more intense tissue response (score: 0.83±0.12 SEM) which can be statistically underscored with a p-value of 0.0133 when compared to the reservoir + PBS group, and p<0.001, when matched with reservoir + DEX. The group treated with the reservoir and PBS (0.47±0.08) also achieved a higher ranking score than the reservoir + DEX treated ones (0.25±0.05 SEM; p<0.05).


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)

Graphed t-test results of tissue growth ranking (A) and measurement (B) for the whole cochlea length.Using both evaluation methods the tissue growth in the trauma group was significantly increased compared to the reservoir and DEX group with a p value <0.001. When applying the ranking score the difference between reservoir + PBS and trauma or reservoir + DEX was significant with p<0.05 (A). Comparing the tissue growth of the reservoir + PBS group with those of the trauma group or the DEX group using the measuring method, the p value is <0.001 (PBS vs. trauma) and <0.05 (PBS vs. DEX). Error bars: SEM. * = p<0.05, *** = p<0.001.
© Copyright Policy
Related In: Results  -  Collection

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

pone-0104564-g004: Graphed t-test results of tissue growth ranking (A) and measurement (B) for the whole cochlea length.Using both evaluation methods the tissue growth in the trauma group was significantly increased compared to the reservoir and DEX group with a p value <0.001. When applying the ranking score the difference between reservoir + PBS and trauma or reservoir + DEX was significant with p<0.05 (A). Comparing the tissue growth of the reservoir + PBS group with those of the trauma group or the DEX group using the measuring method, the p value is <0.001 (PBS vs. trauma) and <0.05 (PBS vs. DEX). Error bars: SEM. * = p<0.05, *** = p<0.001.
Mentions: Using student's t-test the evaluation of fibrotic tissue response in the whole cochlea by use of a subjective scoring system revealed significant differences between the three experimental groups (Fig. 4A). The trauma group suffered from a more intense tissue response (score: 0.83±0.12 SEM) which can be statistically underscored with a p-value of 0.0133 when compared to the reservoir + PBS group, and p<0.001, when matched with reservoir + DEX. The group treated with the reservoir and PBS (0.47±0.08) also achieved a higher ranking score than the reservoir + DEX treated ones (0.25±0.05 SEM; p<0.05).

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