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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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Correlation of hearing loss measured on day 28 and tissue reaction determined by ranking.Graph A illustrates that with the amount of tissue reaction evaluated over the whole cochlea length the loss of residual hearing in all frequencies increases (p<0.001; r = 0.6338). This effect is detectable in lower and higher frequency regions of the cochleae as well. In figure 7B the detected tissue reaction and hearing loss at the upper basal turn and at 32 kHz are plotted as an example for the correlation in higher frequency areas 7B the detected tissue reaction and hearing loss at the upper basal turn and at 32 kHz are plotted as an example for the correlation in higher frequency areas kHz are plotted as an example for the correlation in higher frequency areas (p<0.05; r = 0.3742). Fig. C is an example for correlation of tissue reaction and hearing loss in lower frequency areas of the cochlea. Here we correlated hearing loss at 1 kHz and tissue growth in the 3 kHz and tissue growth in the 3rd middle turn (p<0.05; r = 0.3727).
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pone-0104564-g007: Correlation of hearing loss measured on day 28 and tissue reaction determined by ranking.Graph A illustrates that with the amount of tissue reaction evaluated over the whole cochlea length the loss of residual hearing in all frequencies increases (p<0.001; r = 0.6338). This effect is detectable in lower and higher frequency regions of the cochleae as well. In figure 7B the detected tissue reaction and hearing loss at the upper basal turn and at 32 kHz are plotted as an example for the correlation in higher frequency areas 7B the detected tissue reaction and hearing loss at the upper basal turn and at 32 kHz are plotted as an example for the correlation in higher frequency areas kHz are plotted as an example for the correlation in higher frequency areas (p<0.05; r = 0.3742). Fig. C is an example for correlation of tissue reaction and hearing loss in lower frequency areas of the cochlea. Here we correlated hearing loss at 1 kHz and tissue growth in the 3 kHz and tissue growth in the 3rd middle turn (p<0.05; r = 0.3727).

Mentions: Tissue growth concurred with the results of AABR measurements. A profound correlation between mean values of the amount of tissue, determined by subjective ranking, and the averaged hearing loss of all frequencies of the individual animal was ascertained. It was demonstrated that with increasing tissue growth hearing loss increased (Fig. 7A). Using the Spearman-Rho-tests a correlation with r = 0.6338 (p<0.001) was detected.


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)

Correlation of hearing loss measured on day 28 and tissue reaction determined by ranking.Graph A illustrates that with the amount of tissue reaction evaluated over the whole cochlea length the loss of residual hearing in all frequencies increases (p<0.001; r = 0.6338). This effect is detectable in lower and higher frequency regions of the cochleae as well. In figure 7B the detected tissue reaction and hearing loss at the upper basal turn and at 32 kHz are plotted as an example for the correlation in higher frequency areas 7B the detected tissue reaction and hearing loss at the upper basal turn and at 32 kHz are plotted as an example for the correlation in higher frequency areas kHz are plotted as an example for the correlation in higher frequency areas (p<0.05; r = 0.3742). Fig. C is an example for correlation of tissue reaction and hearing loss in lower frequency areas of the cochlea. Here we correlated hearing loss at 1 kHz and tissue growth in the 3 kHz and tissue growth in the 3rd middle turn (p<0.05; r = 0.3727).
© Copyright Policy
Related In: Results  -  Collection

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

pone-0104564-g007: Correlation of hearing loss measured on day 28 and tissue reaction determined by ranking.Graph A illustrates that with the amount of tissue reaction evaluated over the whole cochlea length the loss of residual hearing in all frequencies increases (p<0.001; r = 0.6338). This effect is detectable in lower and higher frequency regions of the cochleae as well. In figure 7B the detected tissue reaction and hearing loss at the upper basal turn and at 32 kHz are plotted as an example for the correlation in higher frequency areas 7B the detected tissue reaction and hearing loss at the upper basal turn and at 32 kHz are plotted as an example for the correlation in higher frequency areas kHz are plotted as an example for the correlation in higher frequency areas (p<0.05; r = 0.3742). Fig. C is an example for correlation of tissue reaction and hearing loss in lower frequency areas of the cochlea. Here we correlated hearing loss at 1 kHz and tissue growth in the 3 kHz and tissue growth in the 3rd middle turn (p<0.05; r = 0.3727).
Mentions: Tissue growth concurred with the results of AABR measurements. A profound correlation between mean values of the amount of tissue, determined by subjective ranking, and the averaged hearing loss of all frequencies of the individual animal was ascertained. It was demonstrated that with increasing tissue growth hearing loss increased (Fig. 7A). Using the Spearman-Rho-tests a correlation with r = 0.6338 (p<0.001) was detected.

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