The Breakdown of Blood-Labyrinth Barrier Makes it Easier for Drugs to Enter the Inner Ear

Abstract

Purpose: This study aimed to investigate dynamic change of permeability of blood-labyrinth barrier (BLB) after noise exposure and its effect on the drug delivery efficiency of systemic administration.

Methods: Gadopentetate dimeglumine (Gd-DTPA) and dexamethasone (DEX) were used as tracers, and magnetic resonance imaging (MRI) and immunofluorescence were used to observe the change of the BLB after strong noise exposure in guinea pigs. High-performance liquid chromatography-mass spectrometry (LC-MS) was used to observe the effect of the breakdown of BLB after noise exposure on the drug delivery efficiency of intravenous DEX. The guinea pigs were divided into 6 groups: normal group (N), 1, 3, 5, 8, and 12 days after noise exposure groups (P1, P3, P5, P8, P12), with 5 animals in each group.

Results: The BLB changes dynamically after noise exposure. Increased permeability of the blood-endolymph barrier, the endolymph-perilymph barrier, and the blood-nerve barrier was observed at days 1-3, 1-5, and 1-8, respectively, after noise exposure in guinea pigs. Higher drug concentration in the cochlear tissue was obtained by intravenous administration of DEX in guinea pigs during the time window of increased permeability of the BLB.

Conclusion: After noise exposure, the increased BLB permeability makes it easier for drugs to enter the inner ear from blood. In guinea pigs, 1-8 days after strong noise exposure, the drug delivery efficiency of systemic administration increased. After 8 days, the efficiency gradually returned to normal level. 1-8 days after noise exposure may be the best intervention time for systemic administration.

Level of evidence: NA Laryngoscope, 134:2377-2386, 2024.

Keywords: blood‐labyrinth barrier; high‐performance liquid chromatography‐mass spectrometry; inner ear drug delivery; magnetic resonance imaging; noise induced hearing loss.