Transtympanic injection of a liposomal gel loaded with N-acetyl-L-cysteine: A relevant strategy to prevent damage induced by cochlear implantation in guinea pigs?
Résumé
Patients with residual hearing can benefit from cochlear implantation. However, insertion can damage cochlear structures and generate oxidative stress harmful to auditory cells. The antioxidant N-acetyl-L-cysteine (NAC) is a precursor of glutathione (GSH), a powerful endogenous antioxidant. NAC local delivery to the inner ear appeared promising to prevent damage after cochlear implantation in animals. NAC-loaded liposomal gel was specifically 35 designed for transtympanic injection, performed both 3 days before and on the day of surgery. Hearing thresholds were recorded over 30 days in implanted guinea pigs with and without NAC. NAC, GSH, and their degradation products, N,N’-diacetyl-L-cystine (DiNAC) and oxidized glutathione (GSSG) were simultaneously quantified in the perilymph over 15 days in non-implanted guinea pigs. For the first time, endogenous concentrations of GSH and GSSG 40 were determined in the perilymph. Although NAC-loaded liposomal gel sustained NAC release in the perilymph over 15 days, it induced hearing loss in both implanted and non-implanted groups with no perilymphatic GSH increase. Under physiological conditions, NAC appeared poorly stable within liposomes. As DiNAC was quantified at concentrations which were twice as high as NAC in the perilymph, it was hypothesized that DiNAC could be 45 responsible for the adverse effects on hearing.
Mots clés
1
2-dipalmitoyl-sn-glycero-
auditory brainstem response
CI
cochlear implanted
Chol
cholesterol
DiNAC
Dh
hydrodynamic diameter
DL
drug loading
DLS
dynamic light scattering
DPPC
Glutathione
hyaluronic acid
inner ear
local drug delivery
N
N'-diacetyl-L-cystine
oxidative stress ABR
auditory brainstem response CI
cochlear implanted Chol
cholesterol DiNAC
N'-diacetyl-L-cystine Dh
hydrodynamic diameter DL
drug loading DLS
dynamic light scattering DPPC
Domaines
Sciences du Vivant [q-bio]
Fichier principal
IJP NAC Revised version_Jaudoin et al_Article.pdf (1.26 Mo)
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