Intracochlear distribution and accumulation of locally applied Dexamethasone formulations in a large animal model

Introduction Currently, glucocorticoids are commonly used as treatment for a multitude of inner ear disorders. Large animal models with human-like inner ear dimensions can provide valuable insights into intracochlear pharmacokinetics, deepening our understanding of how drugs propagate within the cochlea. In a translational research approach, we topically applied dexamethasone (DEX) to the middle and inner ears of piglets and analyzed its distribution in the porcine cochlea.

Material and Methods Intratympanic (IT) injections of up to 250µl of DEX-P in its liquid form [4mg/ml] or bound to a thermoreversible hydrogel [6% DEX] were carried out in piglets. For direct intracochlear drug delivery, a novel inner ear catheter [40µl DEX-P] was utilized. Subsequently, apical scala tympani perilymph sampling at different time points after application determined the intracochlear DEX-distribution using high-performance liquid chromatography.

Results Overall DEX-concentrations after 2 hours were significantly elevated using the inner ear catheter for drug delivery as opposed to intratympanic injections using the hydrogel (p≤0.0001). The lowest concentrations after 2 hours were measured after administration of fluid DEX-P via an intratympanic injection (p≤0.000.1). After 24 hours, the hydrogel-IT group displayed reduced DEX concentrations in comparison to the sampling conducted after 2 hours (p≤0.0001).

Conclusion Our work presents the first data on glucocorticoid distribution in the inner ear of a large animal model. The similarity of the porcine cochlea to the human inner ear with respect to spatial dimension supports the clinical translation of our findings and can lay the foundation on how the treatment of inner ear disorders can be optimized in the future.

 

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Artikel online veröffentlicht:
19. April 2024