Preclinical evaluation of thermoreversible triamcinolone acetonide hydrogels for drug delivery to the inner ear

Engleder, Elisabeth; Honeder, Clemens; Klobasa, Julia; Wirth, Michael; Arnoldner, Christoph; Gabor, Franz

doi:10.1016/j.ijpharm.2014.05.057

Cited by 40 publications

(17 citation statements)

References 22 publications

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“…The thermoreversible 20% w/v poloxamer 407 hydrogel (BASF SE, Ludwigshafen, Germany) was prepared using the cold-method and loaded with 6% dexamethasone (Gatt-Koller, Absam, Austria) or 30% triamcinolone-acetonide (Fagron, Barsbüttel, Germany), as previously described [13].…”

Section: Methodsmentioning

confidence: 99%

Effects of intraoperatively applied glucocorticoid hydrogels on residual hearing and foreign body reaction in a guinea pig model of cochlear implantation

Honeder

Landegger

Engleder

et al. 2015

Acta Oto-Laryngologica

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Conclusion-The intraoperative application of glucocorticoid-loaded hydrogels seems to cause a reduction in neutrophil infiltration. No beneficial effect on hearing thresholds was detected.Objectives-To evaluate the application of dexamethasone-and triamcinolone-acetonide-loaded hydrogels for effects on hearing-preservation and foreign-body reaction in a guinea pig model for cochlear implantation.Methods-48 guinea pigs (n= 12/group) were implanted with a single channel electrode and intraoperatively treated with 50 µl of a 20% w/v poloxamer 407 hydrogel loaded with 6% dexamethasone or 30% triamcinolone-acetonide, a control hydrogel, or physiological saline. Click-and tone burst-evoked compound action potential thresholds were determined pre-and directly postoperatively as well as on days 3, 7, 14, 21 and 28. At the end of the experiment, temporal bones prepared for histological evaluation by a grinding/polishing technique with the Results-The intratympanic application of glucocorticoid-loaded hydrogels did not improve the preservation of residual hearing in this cochlear implant model. The foreign body reaction to the electrode appeared reduced in the glucocorticoid treated animals. No correlation was found between the histologically described trauma to the inner ear and the resulting hearing thresholdshifts.

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Section: Methodsmentioning

confidence: 99%

Effects of intraoperatively applied glucocorticoid hydrogels on residual hearing and foreign body reaction in a guinea pig model of cochlear implantation

Honeder

Landegger

Engleder

et al. 2015

Acta Oto-Laryngologica

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“…Another advantage of using poloxamers is the ability to deliver low solubility therapeutics. Formation of micelles in the hydrogel facilitates loading of hydrophobic drugs and gel formation (Engleder et al, 2014). Low solubility drugs such as dexamethasone and methylprednisolone are more easily incorporated in the poloxamer hydrogel compared to aqueous solution (Wang et al, 2011).…”

Section: Biomaterials For Local Drug Deliverymentioning

confidence: 99%

Developments in Bio-Inspired Nanomaterials for Therapeutic Delivery to Treat Hearing Loss

Rathnam

Chueng

Yue

et al. 2019

Front. Cell. Neurosci.

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Sensorineural hearing loss affects millions of people worldwide and is a growing concern in the aging population. Treatment using aminoglycoside antibiotics for infection and exposure to loud sounds contribute to the degeneration of cochlear hair cells and spiral ganglion neurons. Cell loss impacts cochlear function and causes hearing loss in ∼ 15% of adult Americans (∼36 million). The number of individuals with hearing loss will likely grow with increasing lifespans. Current prosthesis such as hearing aids and cochlear implants can ameliorate hearing loss. However, hearing aids are ineffective if hair cells or spiral ganglion neurons are severely damaged, and cochlear implants are ineffective without properly functioning spiral ganglion neurons. As such, strategies that alleviate hearing loss by preventing degeneration or promoting cell replacement are urgently needed. Despite showing great promise from in vitro studies, the complexity and delicate nature of the inner ear poses a huge challenge for delivering therapeutics. To mitigate risks and complications associated with surgery, new technologies and methodologies have emerged for efficient delivery of therapeutics. We will focus on biomaterials that allow controlled and local drug delivery into the inner ear. The rapid development of microsurgical techniques in conjunction with novel bio- and nanomaterials for sustained drug delivery appears bright for hearing loss treatment.

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“…The main approaches for local delivery of glucocorticoids into the inner ear are based on injection of polymeric hydrogels onto the round window [16]. Thermoresponsive in situ forming hydrogel containing 20% Poloxamer 407 (Pluronic F127) and 30% triamcinolone acetonide has been recently developed for prolonged intratympanic release of the drug [18].…”

Section: Accepted Manuscriptmentioning

confidence: 99%

Self-assembled nanoformulation of methylprednisolone succinate with carboxylated block copolymer for local glucocorticoid therapy

Kamalov

Dang

Petrova

et al. 2018

Colloids and Surfaces B: Biointerfaces

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A new self-assembled formulation of methylprednisolone succinate (MPS) based on a carboxylated trifunctional block copolymer of ethylene oxide and propylene oxide (TBC-COOH) was developed. TBC-COOH and MPS associated spontaneously at increased concentrations in aqueous solutions to form almost monodisperse mixed micelles (TBC-COOH/MPS) with a hydrodynamic diameter of 19.6 nm, zeta potential of -27.8 mV and optimal weight ratio ∼1:6.3. Conditions for the effective formation of TBC-COOH/MPS were elucidated by comparing copolymers and glucocorticoids with different structure. The micellar structure of TBC-COOH/MPS persisted upon dilution, temperature fluctuations and interaction with blood serum components. TBC-COOH increased antiradical activity of MPS and promoted its intrinsic cytotoxicity in vitro attributed to enhanced cellular availability of the mixed micelles. Intracellular transportation and hydrolysis of MPS were analyzed using optimized liquid chromatography tandem mass spectrometry with multiple reaction monitoring which showed increased level of both MPS and methylprednisolone in neuronal cells treated with the formulated glucocorticoid. Our results identify TBC-COOH/MPS as an advanced in situ prepared nanoformulation and encourage its further investigation for a potential local glucocorticoid therapy.

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Preclinical evaluation of thermoreversible triamcinolone acetonide hydrogels for drug delivery to the inner ear

Abstract: Graphical abstract

Cited by 40 publications

References 22 publications

Effects of intraoperatively applied glucocorticoid hydrogels on residual hearing and foreign body reaction in a guinea pig model of cochlear implantation

Effects of intraoperatively applied glucocorticoid hydrogels on residual hearing and foreign body reaction in a guinea pig model of cochlear implantation

Developments in Bio-Inspired Nanomaterials for Therapeutic Delivery to Treat Hearing Loss

Self-assembled nanoformulation of methylprednisolone succinate with carboxylated block copolymer for local glucocorticoid therapy

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