Abstract
One major reason for the difficulty in the treatment of inner ear disorders is that only a tiny fraction of drug molecules administrated systemically or intratympanically arrive in the inner ear. Several approaches to override this difficulty are discussed. Steroid encapsulated in Stealth-type nano particles made of biodegradable polymer and coated with poly-ethylene glycol was injected intravenously after noise exposure to induce hearing impairment in guinea pigs. Delivery via Stealth particles resulted in a higher tissue concentration of the steroid in the inner ear and better hearing recovery compared to the steroid alone or encapsulated in non-coated nano particles. Lidocaine, a potential tinnitus attenuator, was encapsulated in microparticles made of biodegradable polymer. The microparticles were placed on the round window membrane (RWM) in guinea pigs, and achieved controlled and sustained delivery of lidocaine into the inner ear. Biodegradable gelatin hydrogels saturated with insulin-like growth factor 1 (IGF-1) were placed on the RWM, and showed a protective effect after inner ear damages in rodents. In humans, a phase I/II clinical trial has been completed in which gelatin hydrogels with IGF-1 were applied to the RWM. Patients with sudden onset hearing impairment, in whom treatment with a 7-day systemic steroid failed, were included in the trial. Hearing recovery was better than the historical control (hyperbaric oxygen therapy as a rescue treatment after the failure of systemic steroids), and no major adverse events were observed. The phase II randomized trial to test the effectiveness of the treatment compared to intratympanic steroids is being conducted in 9 institutes in Japan.
