In:
Otology & Neurotology, Ovid Technologies (Wolters Kluwer Health), Vol. 40, No. 7 ( 2019-08), p. e739-e746
Abstract:
The clinical treatment of sudden sensorineural hearing loss currently relies on the administration of steroids, either systemically or via intratympanic injections. Intratympanic injections bypass the hemato-cochlear barrier, reducing its systemic side effects. The efficacy of the injections is limited through rapid drug clearance via the Eustachian tube, and through nonoptimal properties of slow-release drug carriers. A new slow-release drug delivery vehicle based on hexyl-substituted-poly-lactic-acid (HexPLA), with the highest possible safety profile and complete bio-degradability, has been evaluated for safety and efficacy in a standardized guinea pig model of intratympanic injection. Methods: A total of 83 animals received through retrobullar injection either empty Nile-red-colored HexPLA vehicle, 5%-dexamethasone-HexPLA, 5%-dexamethasone suspension, or a sham operation. Long-term residence time of vehicle, biocompatibility, click- and pure-tone hearing thresholds, and dexamethasone levels in the perilymph were prospectively assessed. Results: At 1 week after injection, HexPLA vehicle was morphologically present in the middle ear and perilymph levels in the 5%-dexamethasone-HexPLA were on average 2 to 3 μg/ml and one order of magnitude higher compared with those of the 5%-dexamethasone suspension group. No significant postoperative morphological or functional changes were observed up to 3 months postdelivery. Conclusions: HexPLA is safe, fully biocompatible, and efficient for sustained high-dose, intratympanic delivery of dexamethasone at least for 1 week and therefore of high interest for the treatment of sudden sensorineural hearing loss and other acute inner ear diseases. Due to the favorable chemical properties, a wide range of other drugs can be loaded into the vehicle further increasing its potential value for otological applications.
Type of Medium:
Online Resource
ISSN:
1531-7129
,
1537-4505
DOI:
10.1097/MAO.0000000000002305
Language:
English
Publisher:
Ovid Technologies (Wolters Kluwer Health)
Publication Date:
2019
detail.hit.zdb_id:
2058738-7
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