A Metal-Organic Framework Based Inner Ear Delivery System for the Treatment of Noise-Induced Hearing Loss

Noise-induced hearing loss (NIHL) is associated both acute and chronic noise exposure. The application of steroid hormones is the first-line treatment for NIHL. However, the application of steroid hormone in the body needs high-dose to keep its efficacy and causes side effects, such as headache and osteoporosis. In this work, we have prepared a zeolitic imidazolate framework (ZIF)-based system for steroid hormone delivery in inner ear. Methylprednisolone (MP), a typical steroid hormone, was encapsulated into ZIF-90 nanoparticles (NPs) in one-pot. The obtained MP@ZIF-90 NPs are negatively charged NPs with 120 nm in size, which show good biocompatibility and good stability at pH 7.4. After intraperitoneal injection, ZIF-90 could efficiently protect drugs during the peripheral blood circulation, enter the inner ear by passing the blood labyrinthine barrier (BLB) and slowly release the drugs. Auditory brainstem response (ABR) tests indicate that MP@ZIF-90 exhibits a better protection of mice from noise than those using free MP and ZIF-8 with encapsulated MP (MP@ZIF-8). More importantly, MP@ZIF-90 shows no defect in inner ear after being treated with noise and low nephrotoxicity during therapy, which demonstrates the biocompatibility of this material. We believe ZIF-90 based delivery system is an efficient delivery system for inner ear therapy of NIHL.