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

Cross-section images of silicone tubes before and after filling between 2 and 10 mm with with 20 mm with with 20% (w/v) NCO-sP(EO-stat-PO) gels (top left and middle), after drying of the gel (top right), re-swelling (bottom right) and after maintaining the gels in a swollen condition for 50 days (bottom left).
© Copyright Policy
Related In: Results  -  Collection

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

pone-0104564-g002: Cross-section images of silicone tubes before and after filling between 2 and 10 mm with with 20 mm with with 20% (w/v) NCO-sP(EO-stat-PO) gels (top left and middle), after drying of the gel (top right), re-swelling (bottom right) and after maintaining the gels in a swollen condition for 50 days (bottom left).

Mentions: In this configuration, the open end of the silicone tube is filled hydrogel for a certain length, so as to create a diffusion gate that could possibly separate the inner ear from an externally accessible drug reservoir. We also evaluated the possibility to dry and re-swell the set-up and whether this would lead to a tight fit of the re-swollen gel inside the tubes. Fig. 2 presents a series of images showing cross-sections of silicone tubes before and after filling with gel. In order to evaluate whether the gels remain in the tubes after drying and re-swelling, the gels in the tubes were warmed to 50°C under reduced pressure (100 mbar) for 30 minutes which resulted in a strong shrinkage of the hydrogel. However, the gels remained at the place in the tubes where they had been placed and after re-swelling the gels tightly closed the inner lumen of the tubes without any visible gaps, this being independent of the hydrogel gate length.


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)

Cross-section images of silicone tubes before and after filling between 2 and 10 mm with with 20 mm with with 20% (w/v) NCO-sP(EO-stat-PO) gels (top left and middle), after drying of the gel (top right), re-swelling (bottom right) and after maintaining the gels in a swollen condition for 50 days (bottom left).
© Copyright Policy
Related In: Results  -  Collection

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

pone-0104564-g002: Cross-section images of silicone tubes before and after filling between 2 and 10 mm with with 20 mm with with 20% (w/v) NCO-sP(EO-stat-PO) gels (top left and middle), after drying of the gel (top right), re-swelling (bottom right) and after maintaining the gels in a swollen condition for 50 days (bottom left).
Mentions: In this configuration, the open end of the silicone tube is filled hydrogel for a certain length, so as to create a diffusion gate that could possibly separate the inner ear from an externally accessible drug reservoir. We also evaluated the possibility to dry and re-swell the set-up and whether this would lead to a tight fit of the re-swollen gel inside the tubes. Fig. 2 presents a series of images showing cross-sections of silicone tubes before and after filling with gel. In order to evaluate whether the gels remain in the tubes after drying and re-swelling, the gels in the tubes were warmed to 50°C under reduced pressure (100 mbar) for 30 minutes which resulted in a strong shrinkage of the hydrogel. However, the gels remained at the place in the tubes where they had been placed and after re-swelling the gels tightly closed the inner lumen of the tubes without any visible gaps, this being independent of the hydrogel gate length.

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