Sustained Release Inner Ear Delivery of Corticosteroid

DESCRIPTION (provided by applicant): The long term goal of this research is to reduce or eliminate deafness due to certain diseases of the inner ear by developing sustained release formulations for anti-inflammatory drugs which can be implanted directly into the inner ear. The initial project will be to develop an inner ear delivery system for corticosteroids. The specific aims of this proposal are to: 1, formulate sustained release suspensions of the corticosteroid rimexolone; 2, test the in vitro release characteristics of these formulations into buffer; and 3, test the in vivo pharmacokinetics and the safety of the formulations after implantation into the inner ear of the guinea pig. In previous work, supported in part through SBIR Phase 1 and 2 funding, we have developed the FDA approved intraocular delivery systems Vitrasert(r), and Retisert(r): an implant that delivers therapeutic doses to the inside of the eye for 3 years with a single implantation. The team of investigators is expert in polymer chemistry, pharmacokinetics, drug development, and clinical otology. We have experience in all aspects of the drug development process, from concept to approval and marketing. The successful completion of these specific aims will constitute a readily identifiable milestone which will permit us to continue with Phase 2 of this proposal where we will test the efficacy of the devices in animal models of sensorineural hearing loss and complete the requisite laboratory work to apply for an Investigational New Drug Exemption from the FDA. Many forms of deafness could be treated with drugs; however, most drugs do not penetrate sufficiently into the inner ear and therefore cannot be effective. Because corticosteroids have the potential to treat several diseases, we are developing a sustained release inner ear delivery system for this class of drugs. This system could also be used for other drugs where chronic delivery is essential.