Poly-Lactic Acid-Based Biopolymer Formulations Are Safe for Sustained Intratympanic Dexamethasone Delivery.

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. 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. 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. 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.