To Örebro University

Background: One alternative for controlled drug delivery to the inner ear is application of medication to the middle ear cavity on the promise that it will diffuse through the round window membrane (RWM) into the inner ear.

Objective: to evaluate the efficacy of hyaluronic acid gel (HYA) as a vehicle for drugs that are aimed to treat inner ear disorders.

Methods: in this study the cochlear hair cell loss and RWM morphology were investigated after topical application. Neomycin was chosen as tracer for drug release and the ototoxic effect was evaluated. HYA, (0.5%) loaded with 3 different concentrations of neomycin, was injected to the middle ear cavity of guinea pigs. the ototoxic effect of neomycin in HYA gel was compared to that of neomycin solution applied to the middle ear cavity. Phalloidin stained surface preparation of the organ of Corti was used to estimate hair cell loss induced by neomycin. the thickness of the midportion of the RWM was measured and compared with that of controls using light and electrom microscope.

Result: Neomycin induced a considerable hair cell loss in guinea pigs receiving middle ear injection of HYA loaded with the drug. One week after topical application the thickness of the RWM was dependent upon the concentration of neomycin administered to the middle ear. At 4 weeks the thickness of the RWM had returned to normal.

Conclusion: HYA is a safe vehicle for drugs aimed to pass into the inner ear through the RWM. Neomycin was released from HYA and transported into the inner ear as evidenced by hair cell loss. Key words: Round window membrane (RWM), hyaluronic acid gel, HYA, hair cell loss, thickness.