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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

Mean and SEM of hearing loss (difference between the experimental days hearing threshold and hearing threshold before implantation) development from day 3 to day 28 for all experimental groups.Cochleae of the trauma group (n = 12) suffered from highest hearing loss compared to all other experimental groups. Additionally, individuals implanted with a PBS releasing reservoir (n = 12) lost hearing more significantly compared to the group having been implanted with the DEX filled reservoir (n = 14). The statistical differences using ANOVA test examined on experimental day 28 are plotted at the right side of the graph, demonstrating, that the reservoir + DEX treatment resulted in the significantly best hearing thresholds. (** = p<0.01; *** = p<0.001).
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pone-0104564-g003: Mean and SEM of hearing loss (difference between the experimental days hearing threshold and hearing threshold before implantation) development from day 3 to day 28 for all experimental groups.Cochleae of the trauma group (n = 12) suffered from highest hearing loss compared to all other experimental groups. Additionally, individuals implanted with a PBS releasing reservoir (n = 12) lost hearing more significantly compared to the group having been implanted with the DEX filled reservoir (n = 14). The statistical differences using ANOVA test examined on experimental day 28 are plotted at the right side of the graph, demonstrating, that the reservoir + DEX treatment resulted in the significantly best hearing thresholds. (** = p<0.01; *** = p<0.001).

Mentions: On experimental day 0, prior to surgery, all animals were possessing normal hearing. No significant differences in mean AABR thresholds, given as lowest sound intensity where the brainstem response exceeded the triple standard deviation of the background noise, were observed between experimental groups across all frequencies (data not shown). Postoperatively, all groups suffered from an initial loss of hearing detected in the average of all frequencies measured three days after surgery: the mean ± SEM difference compared to the day 0 threshold was: 8.33±4.52 dB SPL in the reservoir + DEX group, 16.94±7.04 dB SPL in the reservoir + PBS group and 39.03±7.28 dB SPL in the trauma group (Fig. 3).


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)

Mean and SEM of hearing loss (difference between the experimental days hearing threshold and hearing threshold before implantation) development from day 3 to day 28 for all experimental groups.Cochleae of the trauma group (n = 12) suffered from highest hearing loss compared to all other experimental groups. Additionally, individuals implanted with a PBS releasing reservoir (n = 12) lost hearing more significantly compared to the group having been implanted with the DEX filled reservoir (n = 14). The statistical differences using ANOVA test examined on experimental day 28 are plotted at the right side of the graph, demonstrating, that the reservoir + DEX treatment resulted in the significantly best hearing thresholds. (** = p<0.01; *** = p<0.001).
© Copyright Policy
Related In: Results  -  Collection

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

pone-0104564-g003: Mean and SEM of hearing loss (difference between the experimental days hearing threshold and hearing threshold before implantation) development from day 3 to day 28 for all experimental groups.Cochleae of the trauma group (n = 12) suffered from highest hearing loss compared to all other experimental groups. Additionally, individuals implanted with a PBS releasing reservoir (n = 12) lost hearing more significantly compared to the group having been implanted with the DEX filled reservoir (n = 14). The statistical differences using ANOVA test examined on experimental day 28 are plotted at the right side of the graph, demonstrating, that the reservoir + DEX treatment resulted in the significantly best hearing thresholds. (** = p<0.01; *** = p<0.001).
Mentions: On experimental day 0, prior to surgery, all animals were possessing normal hearing. No significant differences in mean AABR thresholds, given as lowest sound intensity where the brainstem response exceeded the triple standard deviation of the background noise, were observed between experimental groups across all frequencies (data not shown). Postoperatively, all groups suffered from an initial loss of hearing detected in the average of all frequencies measured three days after surgery: the mean ± SEM difference compared to the day 0 threshold was: 8.33±4.52 dB SPL in the reservoir + DEX group, 16.94±7.04 dB SPL in the reservoir + PBS group and 39.03±7.28 dB SPL in the trauma group (Fig. 3).

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