Efficiency of a dexamethasone nanosuspension as an intratympanic injection for acute hearing loss

Abstract

Dexamethasone sodium phosphate (Dex-SP) is the most commonly used drug administered via intratympanic injection for the treatment of acute hearing loss, but its penetration efficiency into the inner ear is very low. To address this problem, we evaluated the possibility of administering dexamethasone nanosuspensions via intratympanic injection because hydrophobic drugs might be more effective in penetrating the inner ear. Three types of dexamethasone nanosuspensions were prepared; the dexamethasone nanoparticles in the three nanosuspensions were between approximately 250 and 350 nm in size. To compare the efficiency of Dex-SP and dexamethasone nanosuspension in delivering dexamethasone to the inner ear, the concentrations of dexamethasone in perilymph and cochlear tissues were compared by liquid chromatography–mass spectrometry. The dexamethasone nanosuspensions resulted in significantly higher drug concentrations in perilymph and cochlear tissues than Dex-SP at 6 h; interestingly, animals treated with nanosuspensions showed a 26-fold higher dexamethasone concentrations in their cochlear tissues than animals treated with Dex-SP. In addition, dexamethasone nanosuspension caused better glucocorticoid receptor phosphorylation than Dex-SP both in vitro and in vivo , and in the ototoxic animal model, the nanosuspension showed a significantly better hearing-protective effect against ototoxic drugs than Dex-SP. In the in vivo safety evaluation, the nanosuspension showed no toxicity at concentrations up to 20 mg/mL. In conclusion, a nanosuspension of dexamethasone was able to deliver dexamethasone to the cochlea very safely and efficiently and showed potential as a formula for intratympanic injection.

An Overview of Nanoparticle Drug Delivery for Ototoxin and Noise Mediated Hearing Loss Treatment

“…Figure 3 indicated that NUFS B group showed considerably better hearing at 8 kHz and 16 kHz and very less damage on the organ of corti, because of superior cell membrane permeation and absorption in the tissue than Dex-SP group. 133 Xiao and co-workers synthesized mitochondrial targeting SS31 peptide functionalized GGA loaded poly(lactic-co-glycolic acid) (PLGA) nanocarrier to defend inner hair cell injury caused by gentamicin in zebrafish model. The drug, GGA release profiles of SS31-PEG-PLGA-GGA NPs and PEG-PLGA-GGA NPs specified that amendment of PLGA NPs surface with SS31 peptide did not evocatively change drug release pattern.…”

“…144 Mild or acute noise trauma can be accountable for temporary hearing threshold shift (TTS), [145][146] which can be reversed by regeneration of two different types of hair cell and hearing nerve fiber using glucocorticoid treatment, [147][148] CC BY-NC. 133 whereas overexposure and/ or strong sound vibrations of harmful noise can trigger permanent threshold shift (PTS), resulting to the irreversible HCs regeneration and auditory nerve deterioration, 143,149 Hair cells, especially outer hair cells (OHCs), auditory nerve deterioration, synaptic ribbon reduction and tympanic membrane perforation are the crucial targets of acoustic trauma. [150][151][152] Various studies have evidenced that necrosis and apoptosis detected in the sensory epithelium after exposed to harmful noise trauma, 156 Metal organic framework-based zeolitic imidazolate (ZIF) nano system encapsulated methylprednisolone (MP), MP@ZIF-90 NP was used first time for the treatment of noise-traumatized hearing impairment in preclinical animal model.…”

“…(B) We observed the whole organ of Corti using confocal microscopy, the stereocilia of the deaf-sham group and the Dex-SP group were highly hurt at all frequency, whereas those of NUFS B group displayed less hurt than those of the other two groups. Adapted with permission fromCC BY-NC 133.…”